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List of TP Press Release on Research

List of TP Press Release on Research

Press Release on Research from TPRP

August 23, 2010

-Aminoacyl-tRNA synthetase (aaRS) paralogs with unknown functions exist in various species. Researchers headed by Shigeyuki Yokoyama at RIKEN reported novel 'protein lysylation' by an Escherichia coli lysyl-tRNA synthetase paralog, GenX. X-ray crystallographic analysis showed that the structure of the GenX protein resembles that of a class II aaRS. Further in vitro studies revealed that it specifically aminoacylates the translation elongation factor P (EF-P) with lysine. The shape of the protein substrate mimics that of the L-shaped tRNA, and its lysylation site corresponds to the tRNA 3′ end. Thus, they showed how the aaRS architecture can be adapted to achieve aminoacylation of a specific protein. Moreover, in vivo analyses revealed that EF-P lysylation by GenX is enhanced by YjeK (lysine 2,3-aminomutase paralog), which is encoded next to the EF-P gene, and might convert α-lysyl–EF-P to β-lysyl–EF-P. In vivo analyses indicated that the EF-P modification by GenX and YjeK is essential for cell survival.

Project Code:	Fundamental Biology B5
Project Theme:	Elucidation of the mechanism of high-order cellular functions achieved by non-coding RNAs
Principal Investigator:	Osamu Nureki
News Release:	News Release (in Japanese) from RIKEN & University of Tokyo;
Research Article:	Nature Struct. Molec. Biol., August 22, 2010. A paralog of lysyl-tRNA synthetase aminoacylates a conserved lysine residue in translation elongation factor P. Tatsuo Yanagisawa, Tomomi Sumida, Ryohei Ishii, Chie Takemoto & Shigeyuki Yokoyama. RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama, Japan. PDB ID code: 3A5Y, 3A5Z

August 16, 2010

-The discovery of small molecules that bind to a specific target and disrupt the function of proteins is an important step in chemical biology, especially for poorly characterized proteins. Human pirin is a nuclear protein of unknown function that is widely expressed in punctate subnuclear structures in human tissues. Researchers led by Hiroyuki Osada at RIKEN report the discovery of a small molecule that binds to pirin. They determined how the small molecule bound to pirin by solving the cocrystal structure. Either knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration. Thus, inhibition of pirin by the small molecule has led to a greater understanding of the function of pirin and represents a new method of studying pirin-mediated signaling pathways.

Project Code:	Chemical Regulation C1
Project Theme:	Establishment of Chemical Library and Development of Protein Regulation Technologys
Principal Investigator:	Tetsuo Ngano
News Release:	News Release (in English) from RIKEN; "Small-molecule inhibitor uncovers protein role in melanoma cell migration"
Research Article:	Nature Chemical Biology, August 15, 2010. A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Isao Miyazaki, Siro Simizu, Hideo Okumura, Satoshi Takagi & Hiroyuki Osada. Chemical Library Validation Team, Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, Wako, Saitama, Japan. PDB ID code: 3ACL

August 13, 2010

-The 21st amino acid, selenocysteine (Sec), is assigned to the codon UGA and is biosynthesized on the Sec-specific tRNA (tRNASec). In archaea and eukarya, tRNASec is ligated with serine by seryl-tRNA synthetase (SerRS), the seryl moiety is phosphorylated by O-phosphoseryl-tRNA kinase (PSTK), and the phosphate group is replaced with selenol by Sep-tRNA:Sec-tRNA synthase. PSTK selectively phosphorylates seryl-tRNASec, whereas SerRS ligates serine with both serine-specific tRNA (tRNASer) and tRNASec. Researchers headed by Shigeyuki Yokoyama at RIKEN determined the crystal structures of the tRNASec・PSTK complex. The structures revealed that the small C-terminal domain (CTD) of the PSTK is associated with the characteristic D arms of tRNASec, independently of the N-terminal catalytic domain. The specific interaction between the unique tRNASec D arm and the PSTK CTD accounts for the strict tRNASec selectivity of PSTK and guarantees the UGA-specific encoding of selenocysteine.

Project Code:	Fundamental Biology B5
Project Theme:	Elucidation of the mechanism of high-order cellular functions achieved by non-coding RNAs
Principal Investigator:	Osamu Nureki
News Release:	News Release (in English) from RIKEN & University of Tokyo; "Scientists clarify structural basis for biosynthesis of mysterious 21st amino acid"
Research Article:	Molecular Cell, August 13, 2010. Structural Basis for the Major Role of O-Phosphoseryl-tRNA Kinase in the UGA-Specific Encoding of Selenocysteine. Chiba S, Itoh Y, Sekine SI, Yokoyama S. Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. PDB ID code: 3ADB, 3ADC, 3ADD

August 2, 2010

-Although C-nitroso aromatic compounds have several bioactivities of medicinal interest, the biosynthetic enzymes involved in C-nitrosation have remained unknown until now. Researchers led by Yasuo Ohnishi at the University of Tokyo report the entire biosynthesis pathway of 4-hydroxy-3-nitrosobenzamide in Streptomyces murayamaensis, in which a tyrosinase-like copper-containing monooxygenase is responsible for the C-nitrosation. This finding indicates diverse catalytic functions of tyrosinase-like copper-containing monooxygenases in nature.

Project Code:	Food/Environment A2
Project Theme:	Structure-based functional analysis of key enzymes that can be applied to production of antibiotics and other useful compounds
Principal Investigator:	Yasuo Ohnishi
News Release:	News Release (in Japanese) from University of Tokyo;
Research Article:	Nature Chemical Biology, August 1, 2010. A copper-containing oxidase catalyzes C-nitrosation in nitrosobenzamide biosynthesis. Akio Noguchi, Takeshi Kitamura, Hiroyasu Onaka, Sueharu Horinouchi & Yasuo Ohnishi. Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo, Japan.

July 1, 2010

-Various social behaviors in mice are regulated by chemical signals called pheromones that act through the vomeronasal system. Exocrine gland-secreting peptide 1 (ESP1) is a 7-kDa peptide that is released into male tear fluids and stimulates vomeronasal sensory neurons in female mice. Kazushige Touhara at the University of Tokyo and his colleagues describe the molecular and neural mechanisms that are involved in the decoding of ESP1 signals in the vomeronasal system, which leads to behavioral output in female mice. ESP1 is recognized by a specific vomeronasal receptor, V2Rp5, and the ligand–receptor interaction results in sex-specific signal transmission to the amygdaloid and hypothalamic nuclei via the accessory olfactory bulb. Consequently, ESP1 enhances female sexual receptive behavior upon male mounting (lordosis), allowing successful copulation. In V2Rp5-deficient mice, ESP1 induces neither neural activation nor sexual behavior. These findings show that ESP1 is a crucial male pheromone that regulates female reproductive behavior through a specific receptor in the mouse vomeronasal system.

Project Code:	Food/Environment B1
Project Theme:	Structural and functional analyses of the rodent ESP family
Principal Investigator:	Hiroaki Terasawa
News Release:	News Release (in Japanese) from University of Tokyo;
Media Coverage:	ScienceNow
Research Article:	Nature, July 1, 2010. The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor. Sachiko Haga, Tatsuya Hattori, Toru Sato, Koji Sato, Soichiro Matsuda, Reiko Kobayakawa, Hitoshi Sakano, Yoshihiro Yoshihara, Takefumi Kikusui and Kazushige Touhara. Departmentof Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

May 28, 2010

-The recirculation of leukocytes is essential for proper immune responses. However, the molecular mechanisms that regulate the entry of leukocytes into the lymphatics remain unclear. Atsushi Kumanogoh at Osaka University and his colleagues show that plexin-A1, a principal receptor component for class III and class VI semaphorins, was crucially involved in the entry of dendritic cells (DCs) into the lymphatics. Additionally, they show that the semaphorin Sema3A was required for DC transmigration and that Sema3A produced by the lymphatics promoted actomyosin contraction at the trailing edge of migrating DCs. Their findings not only demonstrate that semaphorin signals are involved in DC trafficking but also identify a previously unknown mechanism that induces actomyosin contraction as these cells pass through narrow gaps.

Project Code:	Medicine/Pharmacology B4
Project Theme:	Structural and functional analysis of semaphorins and their receptors
Principal Investigator:	Atsushi Kumanogoh
News Release:	News Release (in Japanese) from Osaka University;
Research Article:	Nature Immunology, May 30, 2010. Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Hyota Takamatsu, Noriko Takegahara, Yukinobu Nakagawa, Michio Tomura, Masahiko Taniguchi, Roland H Friedel, Helen Rayburn, Marc Tessier-Lavigne, Yutaka Yoshida, Tatsusada Okuno, Masayuki Mizui, Sujin Kang, Satoshi Nojima, Tohru Tsujimura, Yuji Nakatsuji, Ichiro Katayama, Toshihiko Toyofuku, Hitoshi Kikutani & Atsushi Kumanogoh. Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

May 11, 2010

-Ko Shimamoto and his colleagues found that the rice GTPase OsRac1 at the plasma membrane interacts directly with Pit, an NLR protein that confers resistance to the rice blast fungus. OsRac1 contributes to Pit-mediated ROS (reactive oxygen species) production as well as the hypersensitive response and is required for Pit-mediated disease resistance in rice. Furthermore, the active form of Pit induces the activation of OsRac1 at the plasma membrane. Thus, OsRac1 is activated by Pit during pathogen attack and plays a critical role in Pit-mediated immunity in rice.

Project Code:	Food/Environment B6
Project Theme:	Structure and function of environmentally-responsive proteins
Principal Investigator:	Ko Shimamoto
News Release:	News Release (in Japanese) from NAIST;
Research Article:	Cell Host Microbe., May 20, 2010. Activation of a Rac GTPase by the NLR Family Disease Resistance Protein Pit Plays a Critical Role in Rice Innate Immunity. Kawano Y, Akamatsu A, Hayashi K, Housen Y, Okuda J, Yao A, Nakashima A, Takahashi H, Yoshida H, Wong HL, Kawasaki T, Shimamoto K. Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.

April 26, 2010

-For self-assembly of the bacterial flagellum, the flagellar component proteins synthesized in the cytoplasm are exported by the flagellar type III export apparatus to the growing, distal end. Flagellar protein export is highly organized and well controlled. Flagellar-specific chaperones not only facilitate the export of their cognate proteins, as well as prevent their premature aggregation, but also play a role in fine tuning flagellar gene expression to be coupled with the flagellar assembly process. FliT is a chaperone responsible for the export of the filament-capping protein FliD and for negative control of flagellar gene expression by binding to the FlhDC complex. Katsumi Imada and his colleagues at Osaka U. reported the crystal structure of Salmonella FliT. The structural and biochemical analyses reveal that the C-terminal segment of FliT regulates its interactions with the FlhDC complex, FliI, and FliJ, and that its conformational change is responsible for the switch in its binding partners during flagellar protein export.

Project Code:	Fundamental Biology A1
Project Theme:	Structural and functional studies of bacterial type Ⅲ and type Ⅳ protein export systems
Principal Investigator:	Katsumi Imada
News Release:	News Release (in Japanese) from Osaka University;
Research Article:	Proc Natl Acad Sci USA., April 26, 2010. Structural insight into the regulatory mechanisms of interactions of the flagellar type III chaperone FliT with its binding partners. Imada K, Minamino T, Kinoshita M, Furukawa Y, Namba K. Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan. PDB: 3A7M

April 23, 2010

-Hydantoin membrane transporter (Mhp1) mediates the uptake of hydantoins as part of a metabolic salvage pathway for their conversion to amino acids. Researchers led by So Iwata of Kyoto U. already solved the Mhp1 structures of the outward-facing open and substrate-bound occluded conformations. Now, they report the crystal structure of an inward-facing conformation. From analyses of the three structures and molecular dynamics simulations, they proposed a mechanism for the transport cycle in Mhp1, providing the basis of an alternating access mechanism applicable to many transporters of the emerging superfamily.

Project Code:	Fundamental Biology B4
Project Theme:	Membrane transporters: structure and function of important drug targets
Principal Investigator:	So Iwata
News Release:	News Release (in Japanese) from JST - Kyoto U. News Release from U. Leeds;
Research Article:	Science, April 23, 2010. Molecular Basis of Alternating Access Membrane Transport by the Sodium-Hydantoin Transporter Mhp1. Tatsuro Shimamura, Simone Weyand, Oliver Beckstein, Nicholas G. Rutherford, Jonathan M. Hadden, David Sharples, Mark S. P. Sansom, So Iwata, Peter J. F. Henderson, and Alexander D. Cameron. Department of Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-Ku, Kyoto 606-8501, Japan. PDB ID code: 2X79

April 13, 2010

-Cytochrome c oxidase is the terminal oxidase of cellular respiration, which reductively converts molecular oxygen (O₂) to two water molecules coupled to a proton-pumping process. Researchers headed by Shinya Yoshikawa at U. Hyogo probed the O₂ reduction site of cytochrome c oxidase by x-ray structural analyses of CO, NO, and CN∁Ederivatives to investigate the mechanism of the complete reduction of O₂. Their investigations identify critical roles for the O₂ reduction site in stabilizing the O₂-bound form, facilitating a complete reduction of O₂ with minimal production of reactive oxygen species, and providing a gate for effective proton pumping.

Project Code:	Fundamental Biology B3
Project Theme:	3D structural and functional analyses for elucidation of the mechanism of mitochondrial respiration
Principal Investigator:	Shinya Yoshikawa
News Release:	News Release (in Japanese) from U. Hyogo;
Research Article:	Proc Natl Acad Sci USA, April 12, 2010. Bovine cytochrome c oxidase structures enable O2 reduction with minimization of reactive oxygens and provide a proton-pumping gate. Muramoto K, Ohta K, Shinzawa-Itoh K, Kanda K, Taniguchi M, Nabekura H, Yamashita E, Tsukihara T, Yoshikawa S. Department of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigohri, Akoh, Hyogo 678-1297, Japan. PDB ID code: 3AG1, 3AG2, 3AG3, 3AG4

March 31, 2010

-Ken Ishii at Osaka Univ. and his colleagues examined the mechanisms of action for the three different types of influenza virus vaccines (live virus, inactivated whole-virus and split-virus) using mice lacking three types of sensor receptors (TLR7, IPS-1 and ASC). They revealed that TLR7 acted as the adjuvant receptor for the immunogenicity of both live virus and whole-virus vaccines, whereas a split vaccine failed to immunize naïve mice. Furthermore, whole-virus vaccine loaded plasmacytoid dendritic cells are found to be sufficient to transfer immunogenicity to naïve mice, which requires intrinsic as well as extrinsic type I interferon signaling.

Project Code:	Medicine/Pharmacology A1
Project Theme:	Structural analysis of molecules related to the innate immune system
Principal Investigator:	Shizuo Akira, Ken Ishii
News Release:	News Release from Osaka University; "Plasmacytoid Dendritic Cells Delineate Immunogenicity of Influenza Vaccine Subtypes"
Media Coverage:	Business Week
Research Article:	Science Translational Medicine, March 31, 2010. Plasmacytoid Dendritic Cells Delineate Immunogenicity of Influenza Vaccine Subtypes Shohei Koyama, Taiki Aoshi, Takeshi Tanimoto, Yutaro Kumagai, Kouji Kobiyama, Takahiro Tougan, Kazuo Sakurai, Cevayir Coban, Toshihiro Horii, Shizuo Akira, and Ken J. Ishii. Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565 E871, Japan.

March 31, 2010

-Researcher headed by Takashi Kadowaki of the Univ. Tokyo revealed that AdipoR1 has a crucial role in the physiological and pathophysiological significance of adiponectin in muscle, and is involved in mitochondrial function and oxidative stress, glucose and lipid metabolism, and exercise endurance. This study suggests that agonism of AdipoR1, as well as strategies to increase AdipoR1 in muscle, may be logical approaches to providing a new treatment modality for mitochondrial dysfunction, insulin resistance and type 2 diabetes linked to obesity.

Project Code:	Medicine/Pharmacology A6
Project Theme:	Structure-based functional analyses and development of drug intervention in metabolic syndrome and diabetes- AdipoR/AMPK/ACC as key targets
Principal Investigator:	Takashi Kadowaki
News Release:	News Release (in Japanese) from the University of Tokyo;
Research Article:	Nature. 2010 Mar 31. [Epub ahead of print] Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1 Masato Iwabu, Toshimasa Yamauchi, Miki Okada-Iwabu, Koji Sato, Tatsuro Nakagawa, Masaaki Funata, Mamiko Yamaguchi, Shigeyuki Namiki, Ryo Nakayama, Mitsuhisa Tabata, Hitomi Ogata, Naoto Kubota, Iseki Takamoto, Yukiko K. Hayashi, Naoko Yamauchi, Hironori Waki, Masashi Fukayama, Ichizo Nishino, Kumpei Tokuyama, Kohjiro Ueki, Yuichi Oike, Satoshi Ishii, Kenzo Hirose, Takao Shimizu, Kazushige Touhara & Takashi Kadowaki. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8657, Japan.

March 12, 2010

-Recognition of pathogen-associated molecular patterns represents a critical first step of innate defense in plants and animals. Ko Shimamto at NAIST and his colleagues revealed that the rice chitin receptor OsCERK1 interacts with the Hop/Sti1-Hsp90 chaperone complex in the endoplasmic reticulum(ER) and that these chaperons are required for efficient transport of OsCERK1 from the ER to the plasma membrane for chitin-triggered immunity and resistance to rice blast fungus.

Project Code:	Food/Environment B6
Project Theme:	Structure and function of environmentally-responsive proteins
Principal Investigator:	Ko Shimamoto
News Release:	News Release (in Japanese) from NAIST;
Research Article:	Cell Host Microbe. 2010 Mar 18;7(3):185-96. The Hop/Sti1-Hsp90 chaperone complex facilitates the maturation and transport of a PAMP receptor in rice innate immunity. Chen L, Hamada S, Fujiwara M, Zhu T, Thao NP, Wong HL, Krishna P, Ueda T, Kaku H, Shibuya N, Kawasaki T, Shimamoto K. Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology, Takayama, Ikoma, Japan.

January 22, 2010

-Joint research team led by Keiji Tanaka at Tokyo Metropolitan Inst. Medical Science and Masayuki Yamamoto at Tohoku Univ. identifies a novel regulatory mechanism by the selective autophagy substrate p62 of the transcription factor Nrf2 through inactivation of Keap1. An verproduction of p62 or a deficiency in autophagy competes with the interaction between Nrf2 and Keap1, resulting in stabilization of Nrf2 and ranscriptional activation of Nrf2 target genes including antioxidant proteins and detoxification enzymes.

Project:	Fundamental Biology A2: Structural basis for dynamic formation and mechanistic actions of huge and complicated proteolytic machinery(Principal Investigator: Keiji Tanaka) and Fundamental Biology B1: Structural Basis of Sensor System for Cytoprotective Gene Expression Responding to Carcinogens and Oxidative Stress (Principal Investigator: Masayuki Yamamoto)
News Release:	News Release from ST - Tokyo Metropolitan Institute of Medical Science - Tohoku University;
Research Article:	Nat Cell Biol. 2010 Feb 21. [Epub ahead of print] The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motobayashi H, Tanaka K, Yamamoto M. Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan and Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seinyo-cho, Aoba-ku, Sendai 980-8575, Japan. PDB ID code: 3ADE

January 19, 2010

-Keap1 protein represses activity of the transcription factor Nrf2, and acts as a cellular sensor for oxidative stresses. Masayuki Yamamoto of Tohoku University and his colleagues reported the structure of mouse Keap1 homodimer by single particle electron microscopy. Three-dimensional reconstruction at 24-ÁEresolution revealed two large spheres attached by short linker arms to the sides of a small forked-stem structure, resembling a cherry-bob.

Project Code:	Fundamental Biology B1
Project Theme:	Structural Basis of Sensor System for Cytoprotective Gene Expression Responding to Carcinogens and Oxidative Stress
Principal Investigator:	Masayuki Yamamoto
News Release:	News Release from Tohoku University;
Research Article:	Proc Natl Acad Sci USA. 2010 Jan 27. [Epub ahead of print] Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycinerepeat, and C-terminal domains. Ogura T, Tong KI, Mio K, Maruyama Y, Kurokawa H, Sato C, Yamamoto M. Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seinyo-cho, Aoba-ku, Sendai 980-8575, Japan.

January 18, 2010

-Unneeded or damaged proteins are degraded into amino acids which are used in synthesizing new proteins. Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is repeatedly catalyzed by enzymes called ubiquitin ligases, resulting in a polyubiquitin chain. Researchers led by Koichi Kato at Institute for Molecular Science determined crystal structure of the ubiquitin-conjugating enzyme E2  Eubiquitin intermediate state for ubiquitin transfer and provided structural insights into the formation of polyubiquitin chains.

Project Code:	Fundamental Biology A2
Project Theme:	Structural basis for dynamic formation and mechanistic actions of huge and complicated proteolytic machinery
Principal Investigator:	Keiji Tanaka
News Release:	News Release from Institute for Molecular Science;
Research Article:	Structure. 2010 Jan 13;18(1):138-47. Crystal structure of UbcH5b - ubiquitin intermediate: insight into the formation of the self-assembled E2 - Ub conjugates. Sakata E, Satoh T, Yamamoto S, Yamaguchi Y, Yagi-Utsumi M, Kurimoto E, Tanaka K, Wakatsuki S, Kato K. Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. PDB ID code 3A33

November 27, 2009

-Researchers headed by Masaki Yamamoto at RIKEN SPring-8 Center demonstrated the successful generation of the bright micro-focused beam with 1µm width at RIKEN targeted proteins beamline (BL32XU) in SPring-8. The beamline with 1µm width could enable to determine 3-D structures of protein micro-crystals with 10µm size and is scheduled to be available for structural biologists next year.

Project Code:	Structural Analysis C1
Project Theme:	Development of the synchrotron beamlines dedicated to the measurement of micron-size protein crystals
Principal Investigator:	Soichi Wakatsuki
News Release:	News Release from RIKEN;

October 23, 2009

-The phytohormone abscisic acid (ABA) mediates the adaptation of plants to environmental stresses such as drought and regulates developmental signals such as seed maturation. Researchers headed by Masaru Tanokura of the University of Tokyo reported the crystal structures of the ABA receptor PYL1 bound with ABA, and the complex formed by the further binding of ABA-bound PYL1 with a group-A protein phosphatases 2C (ABI1) to reveal the ABA signalling mechanism.

Project Code:	Food/Environment A3
Project Theme:	Structural and functional analyses of transcriptional regulatory proteins useful for breading of drought and heat stress tolerant crops
Principal Investigator:	Masaru Tanokura
News Release:	News Release from the University of Tokyo;
Research Article:	Nature. 2009 Oct 23. [Epub ahead of print] Structural basis of abscisic acid signalling. Miyazono KI, Miyakawa T, Sawano Y, Kubota K, Kang HJ, Asano A, Miyauchi Y, Takahashi M, Zhi Y, Fujita Y, Yoshida T, Kodaira K, Yamaguchi-Shinozaki K, Tanokura M. Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan. PDB ID code 3JRS 3JRQ

October 22, 2009

-Transfer RNAs are transcribed as precursor molecules which are then processed, and can undergo recoding of certain nucleotides to generate a different amino acid specificity. Osamu Nureki at the University of Tokyo and his colleagues show how the bacterial enzyme TilS uniquely recognizes and modifies a precursor tRNA Ile2 toward the mature tRNA coding for isoleucine. They demonstrate how TilS prevents the recognition of tRNAIle2 by MetRS and achieves high specificity for its substrate.

Project Code:	Fundamental Biology B5
Project Theme:	Elucidation of the mechanism of high-order cellular functions achieved by non-coding RNAs
Principal Investigator:	Osamu Nureki
News Release:	News Release from the University of Tokyo;
Research Article:	Nature. 2009 Oct 22;461(7267):1144-8. Structural basis for translational fidelity ensured by transfer RNA lysidine synthetase. Nakanishi K, Bonnefond L, Kimura S, Suzuki T, Ishitani R, Nureki O. Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan PDB ID code 3A2K, 3HJ7

September 25, 2009

-The gene networks that control rice flowering under long-day (LD) conditions are not well understood, even though LD flowering is agronomically important in the northern extremes of rice cultivation including Japan. Ko Shimamoto and his colleagues at Nara Institute of Science and Technology revealed that RFT1 is a florigen gene under LD conditions in rice, while Hd3a acts as a florigen gene under short-day (SD) conditions.

Project Code:	Food/Environment B6
Project Theme:	Structure and function of environmentally-responsive proteins
Principal Investigator:	Ko Shimamoto
News Release:	News Release from Nara Institute of Science and Technology; "Rice utilizes two florigen genes depending on long-day and short-day conditions"
Research Article:	Development. 2009 Oct;136(20):3443-50. Epub 2009 Sep 17. A gene network for long-day flowering activates RFT1 encoding a mobile flowering signal in rice. Komiya R, Yokoi S, Shimamoto K. Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology, Ikoma, Nara 630-0101, Japan

September 16, 2009

-Shigeyuki Yokoyama at RIKEN and his colleagues reported a dialysis-based Escherichia coli cell-free system supplemented with a combination of a steroid detergent and a natural lipid, phosphatidylcholine, for the production of a membrane protein actively integrated into liposomes. This approach might be useful for the high yield production of functional membrane proteins.

Project Code:	Protein Production C1
Project Theme:	Development of Advanced Production Technologies for Target Proteins
Principal Investigator:	Shigeyuki Yokoyama
News Release:	News Release from RIKEN;
Research Article:	Protein Sci. 2009 Sep 10. [Epub ahead of print] Production of functional bacteriorhodopsin by an Escherichia coli cell-free protein synthesis system supplemented with steroid detergent and lipid. Shimono K, Goto M, Kikukawa T, Miyauchi S, Shirouzu M, Kamo N, Yokoyama S. RIKEN Systems and Structural Biology Center, Kanagawa, Japan.

September 14, 2009

-Researchers led by Shigeyuki Yokoyama at RIKEN solved the crystal structures of aTrm5 (tRNA modification enzyme) in complex with its substrate tRNA. The structures revealed that aTrm5 has a mechanism to select L-shaped tRNAs as its substrates, and it thereby functions as a tRNA tertiary structure checkpoint in the tRNA maturation process.

Project Code:	Fundamental Biology B5
Project Theme:	Elucidation of the mechanism of high-order cellular functions achieved by non-coding RNAs
Principal Investigator:	Osamu Nureki
News Release:	News Release from RIKEN and the University of Tokyo;
Research Article:	Nat Struct Mol Biol. 2009 September 13. [Epub ahead of print] Tertiary structure checkpoint at anticodon loop modification in tRNA functional maturation. Goto-Ito S, Ito T, Kuratani M, Bessho Y, Yokoyama S. RIKEN Systems and Structural Biology Center, Kanagawa, Japan. PDB ID code: 2ZZM, 2ZZN

May 15, 2009

-Keiji Tanaka, Tokyo Metropolitan Institute of Medical Science, and his colleagues revealed that novel proteins bind specific subunits of the 19S regulatory particles (RPs) of the 26S proteasome, huge and complicated proteolytic machinery, and that these proteins are bona fide RP chaperones to help mature RPs.

Project Code:	Fundamental Biology A2
Project Theme:	Structural basis for dynamic formation and mechanistic actions of huge and complicated proteolytic machinery
Principal Investigator:	Keiji Tanaka
News Release:	News Release from Tokyo Metropolitan Organization for Medical Research; "Multiple Proteins Assist the Assembly of the 19S Regulatory Particle of the 26S Proteasome"
Research Article:	Cell. 2009 May 14. [Epub ahead of print] Multiple Proteasome-Interacting Proteins Assist the Assembly of the Yeast 19S Regulatory Particle. Saeki Y, Toh-E A, Kudo T, Kawamura H, Tanaka K. Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya, Japan.

May 1, 2009

-Keiji Tanaka, Tokyo Metropolitan Institute of Medical Science, and his colleagues identified Rfu1(Regulator for free ubiquitin chains 1) protein, which functions as an inhibitor of Doa4 (a deubiquitinating enzyme) and regulates intracellular concentrations of monomeric ubiquitins and free ubiquitin chains.

Project Code:	Fundamental Biology A2
Project Theme:	Structural basis for dynamic formation and mechanistic actions of huge and complicated proteolytic machinery
Principal Investigator:	Keiji Tanaka
News Release:	News Release from Tokyo Metropolitan Organization for Medical Research; "An Inhibitor of a Deubiquitinating Enzyme Regulates Ubiquitin Homeostasis"
Media Coverage:	Mainichi
Research Article:	Cell. 2009 May 1;137(3):549-59. An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis. Kimura Y, Yashiroda H, Kudo T, Koitabashi S, Murata S, Kakizuka A, Tanaka K. Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya, Japan.

March 27, 2009

-Researchers headed by Yoshinori Fukui at Kyushu U. revealed, during neutrophil chemotaxis which regulates a variety of biological functions including immune response, that intracellular DOCK2 dynamics were sequentially regulated by two distinct phospholipids.

Project Code:	Medicine/Pharmacology A2
Project Theme:	Drug discovery-oriented analysis for structure and function of DOCK2 signaling molecules
Principal Investigator:	Yoshinori Fukui
News Release:	News Release from JST and Kyushu Univ.; "Deciphering the Molecular Mechanisms during Neutrophil Chemotaxis: DOCK2 Dynamics"
Media Coverage:	Nikkei
Research Article:	Science. 2009 Mar 27. [Epub ahead of print] Sequential Regulation of DOCK2 Dynamics by Two Phospholipids during Neutrophil Chemotaxis Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, Cao Q, Sanematsu F, Kanai M, Hasegawa H, Tanaka Y, Shibasaki M, Kanaho Y, Sasaki T,. Frohman M A, and Fukui Y. Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

March 20, 2009

-Researchers led by Soichi Wakatsuki at High Energy Accelerator Research Organization(KEK) demonstrated that NEMO (NF-κB essential modulator) binding to linear ubiquitin chains plays an important role in the activation of the NF-κB pathway based on structural and functional analyses of the complex.

Project Code:	Fundamental Biology A6
Project Theme:	Structure-function analysis of protein complexes that regulate vesicular traffic
Principal Investigator:	Soichi Wakatsuki
News Release:	News Release from KEK; "Triggering an immune system - Linear Ubiquitin Chains Attach to NEMO to Activate NF-κB"
Research Article:	Cell. 2009 Mar 20;136(6):1098-109. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I. Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki, Japan. PDB ID code 3F89, 2ZVO, and 2ZVN

March 13, 2009

Project Code:	Medicine/Pharmacology A5
Project Theme:	Development of anti-trypanosome drugs targeting nucleic acids and red-ox regulatory pathway
Principal Investigator:	Kiyoshi Kita
News Release:	News Release from the University of Tokyo; "Unusual and unique features in the mitochondrial respiratory enzymes from the Trypanosomatida have been identified, providing researchers with potentially invaluable targets for novel chemotherapeutic agents for Chagas disease and sleeping sickness"
Research Article:	J Biol Chem. 2009 Mar 13;284(11):7255-63. Epub 2009 Jan 2. Novel mitochondrial complex II isolated from Trypanosoma cruzi is composed of 12 peptides including a heterodimeric Ip subunit. Morales J, Mogi T, Mineki S, Takashima E, Mineki R, Hirawake H, Sakamoto K, Omura S, Kita K. Department of Biomedical Chemistry, Graduate School of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.

March 11, 2009

-The novel technology for incorporating an iodine-labeled synthetic amino acid (3-iodo-L-tyrosine) into proteins, developed by Shigeyuki Yokoyama and his colleagues at RIKEN, could contribute to accelerate protein structure analyses.

Project Code:	Protein Production C1
Project Theme:	Development of Advanced Production Technologies for Target Proteins
Principal Investigator:	Shigeyuki Yokoyama
News Release:	News Release from RIKEN; "Iodine-labeled synthetic amino acid accelerates protein structure analyses"
Research Article:	Structure 2009 Mar 11;17(3):335-344 Genetic Encoding of 3-Iodo-l-Tyrosine in Escherichia coli for Single-Wavelength Anomalous Dispersion Phasing in Protein Crystallography Sakamoto K, Murayama K, Oki K, Iraha F, Kato-Murayama M, Takahashi M, Ohtake K, Kobayashi T, Kuramitsu S , Shirouzu M, Yokoyama S RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan PDB ID code 2Z0Z, 2Z10, 2Z11, 2ZXV, and 2ZP1

February 26, 2009

-Researchers led by Ko Shimamoto at the Nara Institute of Science and Technology revealed that the RNA levels of Hda3 gene, encoding a floral activator (florigen), are highly correlated with flowering time, and that allelic variation of Hd1 gene is a main source of flowering time diversity in cultivated rice.

Project Code:	Food/Environment B6
Project Theme:	Structure and function of environmentally-responsive proteins
Principal Investigator:	Ko Shimamoto
News Release:	News Release from Nara Institute of Science and Technology; "Deciphering the Molecular Mechanisms Promoting the Diversity of Flowering Time in Cultivated Rice"
Media Coverage:	Asahi (asahi.com), Sankei (Sankei Digital), Nikkei
Research Article:	Proc Natl Acad Sci U S A. 2009 Feb 25. [Epub ahead of print] Variations in Hd1 proteins, Hd3a promoters, and Ehd1 expression levels contribute to diversity of flowering time in cultivated rice. Takahashi Y, Teshima KM, Yokoi S, Innan H, and Shimamoto K. Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology, Ikoma, Nara 630-0101, Japan PMID: 19246394

February 23, 2009

-Takuya Ueda and his colleagues of U. Tokyo individually synthesized the entire ensemble of Escherichia coli proteins by using an in vitro reconstituted translation system and analyzed the aggregation propensities. A histogram of the solubilities revealed a clear bimodal distribution.

Project Code:	Protein Production C1
Project Theme:	Development of Advanced Production Technologies for Target Proteins
Principal Investigator:	Shigeyuki Yokoyama
News Release:	News Release from Univ. Tokyo; "Bimodal protein solubility distribution of the entire ensemble of Escherichia coli proteins"
Media Coverage:	Biotechnology Japan Online (February 27)
Research Article:	Proc Natl Acad Sci U S A. 2009 Feb 27. [Epub ahead of print] Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins. Niwa T, Ying BW, Saito K, Jin W, Takada S, Ueda T, Taguchi H. Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan PMID: 19251648

February 17, 2009

-Researchers headed by Junn Yanagisawa at the University of Tsukuba have discovered that an enzyme called CHIP, which is known to degrade a number of cancer causing proteins, acts to degrade the gene regulator SRC-3, which then suppresses tumor progression in breast cancer.

Project Code:	Medicine/Pharmacology B2Food/Environment A4
Project Theme:	Development of new compounds for fibrosis therapy
Principal Investigator:	Junn Yanagisawa
News Release:	News Release from Tsukuba Univ.; "CHIP enzyme prevents breast tumor growth and metastasis"
Media Coverage:	Yomiuri, Mainichi, Reuters, ecancermedicalscience
Research Article:	Nat Cell Biol. 2009 Feb 8. [Epub ahead of print] The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways. Kajiro M, Hirota R, Nakajima Y, Kawanowa K, So-Ma K, Ito I, Yamaguchi Y, Ohie SH, Kobayashi Y, Seino Y, Kawano M, Kawabe YI, Takei H, Hayashi SI, Kurosumi M, Murayama A, Kimura K, Yanagisawa J. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan. PMID: 19198599

January 1, 2009

Project Code:	Fundamental Biology B5
Project Theme:	Elucidation of the mechanism of high-order cellular functions achieved by non-coding RNAs
Principal Investigator:	Osamu Nureki
News Release:	News Release from JST and U. Tokyo; "Pyrrolysyl-tRNA synthetase-tRNA structure reveals the molecular basis of orthogonality"
Research Article:	Nature. 2009 Feb 26;457(7233):1163-7. Epub 2008 Dec 31. Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of orthogonality. Nozawa K, O'Donoghue P, Gundllapalli S, Araiso Y, Ishitani R, Umehara T, Soll D, Nureki O. Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan PMID: 19118381 PDB ID code: 2ZNJ, 2ZNI

November 27, 2008

-The structure of receptor GID1 of key plant hormone gibberellin, reported by Makoto Matsuoka, a plant scientist at Nagoya Univ., and Hiroaki Kato, a structural biologist at Kyoto Univ., reveals how the hormone works.

Project Code:	Food/Environment A4
Project Theme:	Structural and functional analyses of regulatory proteins in plant growth and stress resistance, that is useful for improvement of the stress-resistant
Principal Investigator:	Makoto Matsuoka
News Release:	News Release from Nagoya Univ., Kyoto Univ. and RIKEN; "Structure of gibberellin revealed - it could help in designing more potent plant growth regulators for the second green revolution era"
Media Coverage:	Asahi, Yomiuri, Nikkan-Kogyo (November 27), Chemical & Engineering News (December 1)
Research Article:	Nature. 2008 Nov 27;456 (7221)::520-523. Structural basis for gibberellin recognition by its receptor GID1 Shimada A, Ueguchi-Tanaka M, Nakatsu T, Nakajima M, Naoe Y, Ohmiya H, Kato H, Matsuoka M. Bioscience and Biotechnology Center, Nagoya University, Nagoya, Aichi 464-8601, JapanPMID: 19037316 [PubMed - in process] PDB ID code 3EBL and 3ED1

October 16, 2008

Project Code:	Fundamental Biology B5
Project Theme:	Elucidation of the mechanism of high-order cellular functions achieved by non-coding RNAs
Principal Investigator:	Osamu Nureki
News Release:	News Release from U. Tokyo; "Structural transition of protein secretion machinery across membranes"
Research Article:	Nature. 2008 Oct 16;455(7215):988-91. Conformational transition of Sec machinery inferred from bacterial SecYE structures. Tsukazaki T, Mori H, Fukai S, Ishitani R, Mori T, Dohmae N, Perederina A, Sugita Y, Vassylyev DG, Ito K, Nureki O. Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan PMID: 18923527 PDB ID code: 2ZJS, 2ZQP

August 19, 2008

Project Code:	Protein Production C1
Project Theme:	Development of Advanced Production Technologies for Target Proteins.
Principal Investigator:	Shigeyuki Yokoyama
News Release:	News Release from RIKEN and Univ. Tokyo; "Novel fused enzyme which selectively incorporates nonnatural amino acid into proteins - an editing-domain transplanted tyrosyl-tRNA synthetase with enhanced specificity"
Media Coverage:	Nikkei, Nikkei-Sangyo (August 20)
Research Article:	Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13298-303. Epub 2008 Sep 2. Transplantation of a tyrosine editing domain into a tyrosyl-tRNA synthetase variant enhances its specificity for a tyrosine analog. Oki K, Sakamoto K, Kobayashi T, Sasaki HM, Yokoyama S. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. PMID: 18765802 [PubMed - - indexed for MEDLINE]

July 22, 2008

-Researchers at Yokohama City University headed by Yoshio Goshima and Zenro Ikezawa found that semaphorin3a alleviates skin lesions and scratching behavior in mice.

Project Code:	Medicine / Pharmacology B4
Project Theme:	Structural and functional analysis of semaphorins and their receptors.
Principal Investigator:	Atsushi Kumanogoh
News Release:	News Release from Yokohama City University; "Semaphorin3A, a potent inhibitor of neurite outgrowth, is promising in the treatment of atopic dermatitis"
Media Coverage:	Mainichi (July 22)
Research Article:	J Invest Dermatol. 2008 Dec;128(12):2842-9. Epub 2008 Jul 10 Semaphorin3A Alleviates Skin Lesions and Scratching Behavior in NC/Nga Mice, an Atopic Dermatitis Model. Yamaguchi J, Nakamura F, Aihara M, Yamashita N, Usui H, Hida T, Takei K, Nagashima Y, Ikezawa Z, Goshima Y. Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. PMID: 18615113 [PubMed - in process]

June 17, 2008

Project Code:	Fundamental Biology B4
Project Theme:	Towards structure-based design of novel inhibitors for V -ATPase
Principal Investigator:	So Iwata
News Release:	News Release from Japan Science and Technology Agency, RIKEN and Kyoto Univ.; "Transport mechanism at the rotor ring of sodium ion transporting enzyme V-ATPase was elucidated"
Media Coverage:	-
Research Article:	Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8607-12. Epub 2008 Jun 16. Ion binding and selectivity of the rotor ring of the Na+-transporting V-ATPase. Murata T, Yamato I, Kakinuma Y, Shirouzu M, Walker JE, Yokoyama S, Iwata S. Department of Cell Biology, Faculty of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. PMID: 18559856 [PubMed - indexed for MEDLINE] PDB ID code 2CYD

June 17, 2008

-The specific labeling of proteins in living cells using a genetically encodable tag and a small synthetic probe targeting the tag has been created. This new probe reported by Katsumi Matsuzaki, et al. of Kyoto University was featured in several Japanese newspapers.

Project Code:	Chemical Regulation C1
Project Theme:	Establishment of Chemical Library and Development of Protein Regulation Technology
Principal Investigator:	Tetsuo Nagano
News Release:	News Release from Kyoto Univ.; "Quick labeling of drug receptors with diverse fluorophores - highly tractable and promising method for visualization of membrane receptors"
Media Coverage:	Kyoto, Sankei (June 14), Nikkan-Kogyo, Nikkei-Sangyo (June 16)
Research Article:	ACS Chem Biol. 2008 Jun 20;3(6):341-5. Coiled-coil tag--probe system for quick labeling of membrane receptors in living cell. Yano Y, Yano A, Oishi S, Sugimoto Y, Tsujimoto G, Fujii N, Matsuzaki K. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. PMID: 18533657

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