Decoding of genome function and evolution based on the 3D structures of proteins

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 12208006
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagahama Institute of Bio-Science and Technology (2003-2004); Nagoya University (2000-2002)
• Principal Investigator: GO Mitiko Nagahama Institute of Bio-Science and Technology, Faculty of Bio-Science, Professor, バイオサイエンス学部, 教授 (70037290)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Kenichi Nagahama Institute of Bio-Science and Technology, Faculty of Bio-Science, Associate Professor, バイオサイエンス学部, 助教授 (20322737) ; SHIRAI Tsuyoshi Biomolecular Engineering Research Institute, Department of Computational Biology, Senior Research Scientist, 生命情報解析部門, 主任研究員 (00262890) ; SODA Kunitsugu Nagaoka University of Technology, Department of Bioengineering, Professor, 生物系, 教授 (10011686) ; YURA Kei Japan Atomic Energy Research Institute, Center for Fromotion of Computational Science and Engineering, Quantum Bioinformatics Group, Researcher, 計算科学技術推進センター, 副主任研究員 (50252226)
• Project Period (FY): 2000 – 2004
• Keywords: Prediction of genome function / Module / 3D-keynote / Cyanobacterium genome / Human genome annotation / Sugar-protein interaction / Hydrophobic cluster / Alternative splicing

Research Abstract

As a functional prediction method for ORFs inferred in genome sequences, we developed a method to convert structural and functional properties of protein modules into amino acid sequence patterns, called "3D-keynote". Using the method, we inferred a function of ORF, slr0197 from a cyanobacterium genome, which was subsequently verified by collaborative experiments. Furthermore, we made an automatic system to generate 3D-keynotes for each kind of functions and accomplished generations of 196 kinds of 3D-keynotes, whose prediction accuracies were evaluated to be about 85% on an average. Applying these to a cyanobacterium genome, we obtained clues for inferring the functions for about 12% of function-unknown ORFs. The 3D-keynotes were also used for human genome annotation in H-invitational (Yura ＆ Go).
A sugar-protein interaction prediction system was developed. Strict and loose evaluations of the prediction accuracy resulted in 25 and 66%, respectively, which were better than other existin g methods. To experimentally verify the prediction system, crystal structure analyses of sugar-binding proteins such as lectin, were done. We determined structures of six novel complex forms of congerin and obtained evidences supporting the existence of sugar-binding sites predicted by the prediction system (Shirai).
A chain topology of hydrophobic cluster residues was found to be a reduced representation of a whole chain of the protein molecule. From molecular dynamics simulations of a pseudo-peptide chain composed of hydrophobic cluster residues and cluster analyses of the generated structures, we defined roles of hydrophobic cluster residues as their non-specific hydrophobic aggregation forces made the protein chain compact to decrease the search space for conformations and accelerate the folding process (Soda).
Exhaustively analyzing human full-length cDNA data by the method we developed to identify alternative splicing (AS) regions, we found that most regions altered by AS were shorter than common sizes of protein domains, and indicated possibilities that AS of transcripts may lead to structural destabilization of and/or loss of interaction sites on their protein products and result in changing pathways of the protein network involved (Go ＆ Takahashi).

Research Products

• [Journal Article] An empirical approach for detecting nucleotide-binding sites on proteins. (2006)
  • Author(s): Saito, M., Go, M., Shirai, T.
  • Journal Title: Protein Eng Des Sel. 19 (2) Pages: 67-75
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] "structure and properties of water ", "models for water molecules", "hydration of biomolecules ", "structural analysis of nonnative status ", "structural fluctuation and experimentally observable quantities" (2006)
  • Author(s): Soda, K.
  • Journal Title: Bioinformatics Jiten, Nihon Bioinfprmatics Gakkai-hen (Kyoritsu Syuppan Co.Ltd.) (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vitro evolutionary thermostabilization of congerin II : a limited reproduction of natural protein evolution by artificial selection pressure. (2005)
  • Author(s): Shionyu-Mitsuyama, C., Ito, Y., Konno, A., Miwa, Y., Ogawa, T., Muramoto, K., Shirai, T.
  • Journal Title: J. Mol. Biol. 347 Pages: 385-397
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An empirical approach for detecting nucleotide-binding sites on proteins. (2005)
  • Author(s): Saito, M., Go, M., Shirai, T.
  • Journal Title: Protein Eng Des Sel. 19(2) Pages: 67-75
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vitro evolutionary thermostabilization of congerin II : a limited reproduction of natural protein evolution by artificial selection pressure. (2005)
  • Author(s): Shionyu-Mitsuyama, C., Ito, Y., Konno, A., Miwa, Y., Ogawa, T., Muramoto, K., Shirai, T.
  • Journal Title: J.Mol.Biol. 347 Pages: 385-397
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Post-genome Era and Importance of Protein Thermodynamics (2005)
  • Author(s): Soda, K.
  • Journal Title: NetsuSokutei 32 Pages: 7-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 4.1 physical interaction (2005)
  • Author(s): Soda, K.(Joint Contribution)
  • Journal Title: Tanpakushitsu Kagaku (Kagaku-Dojin Publishing Co.Inc) Pages: 171-183
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Integrative annotation of 21,037 human genes validated by full-length cDNA clones (2004)
  • Author(s): Imanishi, T. et al.
  • Journal Title: PLoS Biology 2(6) Pages: 856-875
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Structure and function of a family 10 beta-xylanase chimera of Streptomyces olivaceoviridis E-86 FXYN and Cellulomonas fimi Cex. (2004)
  • Author(s): Kaneko, S. et al.
  • Journal Title: J. Biol. Chem. 279 Pages: 26619-26626
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Het-PDB Navi. : A database for protein-small molecule interactions. (2004)
  • Author(s): Yamaguchi, A., Iida, K., Matsui, N., Tomoda, S., Yura, K., Go, M.
  • Journal Title: J. Biochem. (Tokyo) 135 Pages: 79-84
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Integrative annotation of 21,037 human genes validated by full-length cDNA clones (2004)
  • Author(s): Imanishi T et al.
  • Journal Title: PLoS Biology 2(6) Pages: 856-875
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Structure and function of a family 10 beta-xylanase chimera of Streptomyces olivaceoviridis E-86 FXYN and Cellulomonas fimi Cex. (2004)
  • Author(s): Kaneko, S., Ichinose, H., Fujimoto, Z., Kuno, A., Yura, K., Go, M., Mizuno, H., Kusakabe, I., Kobayashi, H.
  • Journal Title: J.Biol.Chem. 279 Pages: 26619-26626
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Het-PDB Navi. : A database for protein-small molecule interactions (2004)
  • Author(s): Yamaguchi, A., Iida, K., Matsui, N., Tomoda, S., Yura, K., and, Go, M.
  • Journal Title: J.Biochem. (Tokyo) 135 Pages: 79-84
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enlarged FAMSBASE : protein 3D structure models of genome sequences for 41 species. (2003)
  • Author(s): Yamaguchi, A., Iwadate, M., Suzuki, E., Yura, K., Kawakita, S., Umeyama, H., Go, M.
  • Journal Title: Nucleic Acids Research 31 Pages: 463-468
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An empirical approach for structure-based prediction of carbohydrate-binding sites on proteins. (2003)
  • Author(s): Shionyu-Mitsuyama, C., Shirai, T., Ishida, H., Yamane, T.
  • Journal Title: Protein. Engng. 16 Pages: 467-478
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Crystallization and preliminary X-ray study of α-glucosidase from Geobacill us sp. strain HTA-462, one of the deepest sea bacteria. (2003)
  • Author(s): Shirai, T., Hung, V.-S., Akita, M., Hatada, Y., Ito, S., Horikoshi, K.
  • Journal Title: Acta Cryst. D 59 Pages: 1278-1279
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Translated products of tandem microgene repeats exhibit diverse properties also seen in natural proteins. (2003)
  • Author(s): Shiba, K., Shirai, T., Homma, T., Noda, T.
  • Journal Title: Protein. Engng. 16 Pages: 57-63
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The speciation of conger eel galectins by rapid adaptive evolution. (2003)
  • Author(s): Ogawa, T., Shirai, T., Shionyu-Mitsuyama, C., Yamane, T., Kamiya, H., Muramoto, K.
  • Journal Title: Glyco. J. 19 Pages: 451-458
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Structural Stability and Solution Structure of Chaperonin GroES Heptamer Studied by Synchrotron Small-angle X-ray Scattering (2003)
  • Author(s): Higurashi, T, Hiragi, Y., Ichimura, K., Seki, Y., Soda, K., Mizobata, T., Kawata, Y.
  • Journal Title: J. Mol. Biol. 333 Pages: 605-620
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyl transferase; which has dual enzymatic activities. (2003)
  • Author(s): Yada, T. et al.
  • Journal Title: J. Bio.l Chem. 278(32) Pages: 30235-30247
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinct Interaction of Versican/PG-M with Hyaluronan and Link Protein. (2003)
  • Author(s): Matsumoto, K., Shionyu, M, Go, M., Shimizu, K., Shinomura, T., Kimata K., Watanabe, H.
  • Journal Title: J. Biol. Chem. 278(42) Pages: 41205-41212
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Enlarged FAMSBASE : protein 3D structure models of genome sequences for 41 species (2003)
  • Author(s): Yamaguchi, A., Iwadate, M., Suzuki, E., Yura, K., Kawakita, S., Umeyama, H., Go, M.
  • Journal Title: Nucleic Acids Research 31 Pages: 463-468
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An empirical approach for structure-based prediction of carbohydrate-binding sites on proteins (2003)
  • Author(s): Shionyu-Mitsuyama, C., Shirai, T., Ishida, H., Yamane, T.
  • Journal Title: Protein.Engng. 16 Pages: 467-478
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Crystallization and preliminary X-ray study of a-glucosidase from Geobacillus sp. strain HTA-462, one of the deepest sea bacteria (2003)
  • Author(s): Shirai, T., Hung, V.-S., Akita, M., Hatada, Y., Ito, S., Horikoshi, K.
  • Journal Title: Acta Cryst.D 59 Pages: 1278-1279
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Translated products of tandem microgene repeats exhibit diverse properties also seen in natural proteins (2003)
  • Author(s): Shiba, K., Shirai, T., Homma, T., Noda, T.
  • Journal Title: Protein.Engng. 16 Pages: 57-63
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The speciation of conger eel galectins by rapid adaptive evolution (2003)
  • Author(s): Ogawa, T., Shirai, T., Shionyu-Mitsuyama, C., Yamane, T., Kamiya, H., Muramoto, K.
  • Journal Title: Glyco. J. 19 Pages: 451-458
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Structural Stability and Solution Structure of Chaperonin GroES Heptamer Studied by Synchrotron Small-angle X-ray Scattering (2003)
  • Author(s): Higurashi, T, Hiragi, Y., Ichimura, K., Seki, Y., Soda, K., Mizobata, T., Kawata, Y.
  • Journal Title: J.Mol.Biol. 333 Pages: 605-620
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities. (2003)
  • Author(s): Yada, T., Gotoh, M., Sato, T., Shionyu, M., Go, M., Kaseyama, H., Iwasaki, H., Kikuchi, N., Kwon, Y.D., Togayachi, A., Kudo, T., Watanabe, H., Narimatsu, H., Kimata, K.
  • Journal Title: J.Biol.Chem. 278 (32) Pages: 30235-30247
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distinct Interaction of Versican/PG-M with Hyaluronan and Link Protein. (2003)
  • Author(s): Matsumoto, K., Shionyu, M., Go, M., Shimizu, K., Shinomura, T., Kimata K., Watanabe, H.
  • Journal Title: J.Biol.Chem 278(42) Pages: 41205-41212
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Changes of protein structure and function on accelerated evolution : a case of fish galectin (2003)
  • Author(s): Shirai, T., Shionyu-Mitsuyama, C., Ogawa, T.
  • Journal Title: Tanpakushitsu Kakusan Kouso 48 Pages: 1913-1919
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Crystal structure of a conger eel galectin (congerin II) at 1.45 A resoluti on : Implication for the accelerated evolution of a new ligand-binding site following gene duplication. (2002)
  • Author(s): Shirai, T. et al.
  • Journal Title: J. Mol. Biol. 322 Pages: 879-889
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Adaptive evolution of conger eel galectins. (2002)
  • Author(s): Ogawa, T., Shirai, T., Yamane, T., Muramoto, K.
  • Journal Title: Trend Glyco. 14 Pages: 177-187
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Direct Detection of the Protein Quaternary Structure and Denatured Entity by a Small-Angle Scattering Method : Guanidine Hydrochloride Denaturation of Chaperonin Protein GroEL (2002)
  • Author(s): Hiragi, Y., Seki, Y., Ichimura, K., Soda, K.
  • Journal Title: J. Appl. Cryst. 35 Pages: 1-7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of Solvent Water to the Solution X-ray Scattering Profile of Proteins (2002)
  • Author(s): Seki, Y., Tomizawa, T., Khechinashvili, N.N., Soda, K.
  • Journal Title: Biophys. Chem. 95 Pages: 235-252
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Crystal structure of a conger eel galectin (congerin II) at 1.45 A resolution : Implication for the accelerated evolution of a new ligand-binding site following gene duplication (2002)
  • Author(s): Shirai, T., Matsui, Y., Shionyu-Mitsuyama, C., Yamane, T., Kamiya, H., Ishii, C., Ogawa, T., Muramoto, K.
  • Journal Title: J.Mol.Biol. 322 Pages: 879-889
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adaptive evolution of conger eel galectins (2002)
  • Author(s): Ogawa, T., Shirai, T., Yamane, T., Muramoto, K.
  • Journal Title: Trend Glyco. 14 Pages: 177-187
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Direct Detection of the Protein Quaternary Structure and Denatured Entity by a Small-Angle Scattering Method : Guanidine Hydrochloride Denaturation of Chaperonin Protein GroEL (2002)
  • Author(s): Hiragi, Y., Seki, Y., Ichimura, K., Soda, K.
  • Journal Title: J.Appl.Cryst. 35 Pages: 1-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of Solvent Water to the Solution X-ray Scattering Profile of Proteins (2002)
  • Author(s): Seki, Y., Tomizawa, T., Khechinashvili, N.N., Soda, K.
  • Journal Title: Biophys.Chem. 95 Pages: 235-252
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 3D-keynote : genome function prediction based on protein module (2002)
  • Author(s): Yura, K., Go, M.
  • Journal Title: Tanpakushitsu Kakusan Kouso 47 (8) Pages: 1090-1096
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Protein-Fold Evolution and Protein Structure Predictions (2002)
  • Author(s): Shirai, T.
  • Journal Title: Journal of the Crystallographic Society of Japan 44 Pages: 20-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Capacity of Thermoonospora alba XylA to impart thermostability in family F/10 chimeric xylanases. (2001)
  • Author(s): Ahsan M.M., Kaneko, S., Wang, Q., Yura, K., Go, M., Hayashi K.
  • Journal Title: Enzyme Microb. Technol. 28 Pages: 8-15
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mutational analysis of genes involved in pilus structure, motility and transformation competency in the unicellular motile cyanobacterium Synechoc ystis sp. PCC 6803. (2001)
  • Author(s): Yoshihara, S., Geng, X.X., Okamoto, S., Yura, K., Murata, T., Go M., Ohmori, M., Ikeuchi, M.
  • Journal Title: Plant Cell Physiol. 42 Pages: 63-73
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Crystal structure of alklaine cellulase K : insight into the alkaline adaptation of an industrial enzyme. (2001)
  • Author(s): Shirai, T., Ishida, H., Noda, J., Yamane, T., Ozaki, K., Hakamada, Y., Tto.S.
  • Journal Title: J. Mol. Biol. 310 Pages: 1079-1087
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Variable subunit contact and cooperativity of hemoglobins (2001)
  • Author(s): Shionyu, M., Takahashi, K., Go, M.
  • Journal Title: J. Mol. Evol. 53 Pages: 416-429
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Capacity of Thermoonospora alba XylA to impart thermostability in familyF/10 chimeric xylanases (2001)
  • Author(s): Ahsan M.M., Kaneko, S., Wang, Q., Yura, K., Go, M., Hayashi K.
  • Journal Title: Enzyme Microb. Technol. 28 Pages: 8-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mutational analysis of genes involved in pilus structure, motility and transformation competency in the unicellular motile cyanobacterium Synechocystis sp. PCC 6803 (2001)
  • Author(s): Yoshihara, S., Geng, X.X., Okamoto, S., Yura, K., Murata, T., Go M., Ohmori, M., Ikeuchi, M.
  • Journal Title: Plant Cell Physiol. 42 Pages: 63-73
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Crystal structure of alklaine cellulase K : insight into the alkaline adaptation of an industrial enzyme (2001)
  • Author(s): Shirai, T., Ishida, H., Noda, J., Yamane, T., Ozaki, K., Hakamada, Y., Ito, S.
  • Journal Title: J.Mol.Biol. 310 Pages: 1079-1087
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Variable subunit contact and cooperativity of hemoglobins (2001)
  • Author(s): Shionyu, M., Takahashi, K., Go, M.
  • Journal Title: J.Mol.Evol. 53 Pages: 416-429
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Module shuffling of a family F/10 xylanase : replacement of modules M4 and M5 of the FXYN of Streptomyces olivaceoviridis E-86 with those of the Cex of Cellulomonas fimi. (2000)
  • Author(s): Kaneko, S. et al.
  • Journal Title: Protein Engng. 13 Pages: 873-879
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Significance of a two-domain structure in subunits of phycobiliproteins revealed by the normal mode analysis. (2000)
  • Author(s): Kikuchi, H., Wako, H., Yura, K., Go, M., Mimuro, M.
  • Journal Title: Biophysical Journal 79 Pages: 1587-1600
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Module shuffling of a family F/10 xylanase : replacement of modules M4and M5 of the FXYN of Streptomyces olivaceoviridis E-86 with those of the Cex of Cellulomonas fimi. (2000)
  • Author(s): Kaneko, S., Iwamatsu, S., Kuno, A., Fujimoto, Z., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Hasegawa, T., Kusakabe, I., Hayashi, K.
  • Journal Title: Protein Engng. 13 Pages: 873-879
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Significance of a two-domain structure in subunits of phycobiliproteins revealed by the normal mode analysis (2000)
  • Author(s): Kikuchi, H., Wako, H., Yura, K., Go, M., Mimuro, M.
  • Journal Title: Biophysical Journal 79 Pages: 1587-1600
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] "水の構造と特性","水分子のモデル","生体分子の水和","非天然状態の構造解析","揺らぎと実験観測量",バイオインフォマティクス事典(日本バイオインフォマティクス学会編) (2006)
  • Author(s): 曽田 邦嗣
  • Publisher: 共立出版(in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] ポストゲノム時代と蛋白質分子熱力学の重要性 (2005)
  • Author(s): 曽田 邦嗣
  • Total Pages: 7-12
  • Publisher: 熱測定 32
  • Description: 「研究成果報告書概要(和文)」より
• [Book] "4.1物理的相互作用",タンパク質科学(後藤祐児・桑島邦博・谷澤克行編) (2005)
  • Author(s): 曽田 邦嗣
  • Total Pages: 171-183
  • Publisher: 化学同人
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 加速塩基置換による蛋白質の機能・構造の進化 (2003)
  • Author(s): 白井 剛, 塩生-光山くらら, 小川智久
  • Total Pages: 1913-1919
  • Publisher: 蛋白質核酸酵素,48
  • Description: 「研究成果報告書概要(和文)」より
• [Book] モジュールに基づく機能予測-3Dキーノート (2002)
  • Author(s): 由良 敬, 郷 通子
  • Total Pages: 1090-1096
  • Publisher: 蛋白質核酸酵素 47(8)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 日本結晶学会誌,44 (2002)
  • Author(s): 白井 剛
  • Total Pages: 20-24
  • Publisher: タンパク質の構造予測とフォールド進化
  • Description: 「研究成果報告書概要(和文)」より