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2012 Fiscal Year Final Research Report

Structural studies of a novel mediator regulating homologous recombination

Research Project

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Project/Area Number 22370045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

SHIMIZU Toshiyuki  東京大学, 大学院・薬学系研究科, 教授 (30273858)

Project Period (FY) 2010 – 2012
Keywords相同組み換え / メディエーター / リコンビナーゼ / X線結晶構造解析
Research Abstract

Rad51 has a central role in recombination, assembling onto single-stranded DNA as a nucleoprotein filament and catalyzing the invasion and exchange of homologous DNA sequences. Generally, Rad51 requires the assistance of mediators to overcome the inhibition by RPA. The Swi5-Sfr1 complex has been identified as a mediator, and recent studies have shown that it can activate recombinases directly, and thus this complex is the first molecule for the recombinase activator.We describe the crystal structure of the C-terminal half of Sfr1 in complex with Swi5 from S. pombe. Swi5 and Sfr1 form a parallel coiled-coil heterodimer, joined firmly together by formation of two newly identified leucine-zipper motifs and a bundle. Remarkably, the coiled-coil is sharply kinked, generating an elongated and curved shape. This molecular shape is suitable for binding within the reconstituted helical groove of the Rad51 filament, causing the activation of Rad51 filament by stabilizing it as an active form with a longer helical pitch. Biochemical analysis shows that the C-terminal region of Sfr1 complexed with Swi5 possesses the essential function of Swi5-Sfr1 for a recombination activator, while the N-terminal region of Sfr1 plays a role for the efficient recruitment of the Swi5-Sfr1 complex. Swi5-Sfr1 is conserved from yeast to humans, and therefore the phenomena presented here would be prevalent among all eukaryotic organisms.

  • Research Products

    (13 results)

All 2013 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Characterisation of an intrinsically disordered protein complex of Swi5-Sfr1 by ion mobility mass spectrometry and small-angle X-ray scattering2013

    • Author(s)
      Saikusa K, Kuwabara N, Kokabu Y, Inoue Y, Sato M, Iwasaki H, Shimizu T, Ikeguchi M, Akashi S
    • Journal Title

      Analyst

      Volume: 138 Pages: 1441-1449

    • Peer Reviewed
  • [Journal Article] Mechanistic insights into the activation of rad51-mediated strand exchange from the structure of a recombination activator, the swi5-sfr1 complex2012

    • Author(s)
      Kuwabara N, Murayama Y, Hashimoto H, Kokabu Y, Ikeguchi M, Sato M, Mayanagi K, Tsutsui Y, Iwasaki H, Shimizu T
    • Journal Title

      Structure

      Volume: 20 Pages: 440-449

    • Peer Reviewed
  • [Journal Article] Crystal Structure of Human β-Galactosidase: The Structural Basis of GM1 Gangliosidosis and Morquio B Diseases2012

    • Author(s)
      Ohto U, Usui K, , Ochi T, ,Yuki K, Satow Y andShimizu T
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 1801-1812

    • Peer Reviewed
  • [Journal Article] The fission yeast Swi5-Sfr1 complex, an activator of Rad51 recombinase, forms an extremely elongated Dogleg-shaped structure2011

    • Author(s)
      Kokabu Y, Murayama Y, Kuwabara N, Oroguchi T, Hashimoto H, Tsutsui Y, Nozaki N, Akashi S, Unzai S, Shimizu T, Iwasaki H, Sato M, Ikeguchi M
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 43569-76

    • Peer Reviewed
  • [Journal Article] Crystal Structures of Mouse and Human RP105/MD-1 Complexes Reveal Unique Dimer Organization of the Toll-Like Receptor Family2011

    • Author(s)
      Ohto U, Miyake K, Shimizu T
    • Journal Title

      J Mol Biol

      Volume: 413 Pages: 815-825

    • Peer Reviewed
  • [Journal Article] Expression, Purification and crystallization of Swi5 and the Swi5-Sfr1 complex from fission yeast2010

    • Author(s)
      Kokabu Y, Murayama Y, Kuwabara N, Oroguchi T, Hashimoto H, Tsutsui Y, Nozaki N, Akashi S, Unzai S, Shimizu T, Iwasaki H, Sato M, Ikeguchi M
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 43569-76

    • Peer Reviewed
  • [Journal Article] The structure of the N-terminal regulatory domain of a plant NADPH oxidase and its functional implications2010

    • Author(s)
      Kuwabara, N., Hashimoto, H., Yamada, N., Unzai, S., Ikeguchi, M., Sato, M., Murayama, Y., Iwasaki, H. and Shimizu, T.
    • Journal Title

      Acta Crystallogr

      Volume: F66 Pages: 1124-1126

    • Peer Reviewed
  • [Journal Article]

    • Author(s)
      Oda, T., Hashimoto, H., Kuwabara, N., Akashi, S., Hayashi, K., Kojima, C., Wong, H.L., Kawasaki, T., Shimamoto, K., Sato, M., and Shimizu, T
    • Journal Title

      J.Biol.Chem

      Volume: 285 Pages: 1435-1445

    • Peer Reviewed
  • [Presentation] New frontier of the research in RecAfamily recombinases and their accessory proteins (RecA family 2012)2012

    • Author(s)
      Toshiyuki Shimizu
    • Organizer
      Structural study of recombination activator, Swi5-Sfr1 complex
    • Place of Presentation
      Kyoto Royal Hotel & Spa, Kyoto, Japan
    • Year and Date
      20121128-30
  • [Presentation] Program for Young Researcher Symposium inEurope'SGC Oxford2012

    • Author(s)
      Toshiyuki Shimizu
    • Organizer
      Mechanistic insights into the activation of the Rad51-mediated strand exchange from the structure of recombination activator, Swi5-Sfr1 complex
    • Place of Presentation
      Oxford, UK
    • Year and Date
      2012-06-08
  • [Presentation] New frontier of the research in Rad51 recombinase and its accessory proteinsInstitut de Biologie Physico Chimique2011

    • Author(s)
      Toshiyuki Shimizu
    • Organizer
      Crystal structure of recombination activator, Swi5-Sfr1 complex, from fission yeast
    • Place of Presentation
      France
    • Year and Date
      20110927-28
  • [Presentation] Symposium on Structure and Folding of Disease Related Proteins2011

    • Author(s)
      Toshiyuki Shimizu
    • Organizer
      Mechanistic insights into the activation of the Rad51-mediated strand exchange from the structure of a recombination activator, the Swi5-Sfr1 complex
    • Place of Presentation
      Seoul National University, Korea
    • Year and Date
      2011-07-08
  • [Remarks]

    • URL

      http://www.f.u-tokyo.ac.jp/~kouzou/

URL: 

Published: 2014-08-29  

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