論文

査読有り
2018年3月

Molecular basis for diversification of yeast prion strain conformation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Ohhashi, Yumiko
  • ,
  • Yamaguchi, Yoshiki
  • ,
  • Kurahashi, Hiroshi
  • ,
  • Kamatari, Yuji O.
  • ,
  • Sugiyama, Shinju
  • ,
  • Uluca, Boran
  • ,
  • Piechatzek, Timo
  • ,
  • Komi, Yusuke
  • ,
  • Shida, Toshinobu
  • ,
  • Mueller, Henrik
  • ,
  • Hanashima, Shinya
  • ,
  • Heise, Henrike
  • ,
  • Kuwata, Kazuo
  • ,
  • Tanaka, Motomasa

115
10
開始ページ
2389
終了ページ
2394
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1715483115
出版者・発行元
NATL ACAD SCIENCES

Self-propagating beta-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. When the hidden local microstructures were relaxed by genetic mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid conformation, which redirected chaperone-mediated fiber fragmentation and modulated prion strain phenotypes. Thus, dynamic conformational fluctuations in natively disordered monomeric proteins represent a post-translational mechanism for diversification of aggregate structures and cellular phenotypes.

Web of Science ® 被引用回数 : 17

リンク情報
DOI
https://doi.org/10.1073/pnas.1715483115
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000426671900066&DestApp=WOS_CPL

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