Journal Article

FZJ-2018-07282

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular basis for diversification of yeast prion strain conformation

Ohhashi, Y. ; Yamaguchi, Y. ; Kurahashi, H. ; Kamatari, Y. O. ; Sugiyama, S. ; Uluca, B.FZJ* ; Piechatzek, T. ; Komi, Y. ; Shida, T. ; Müller, H. ; Hanashima, S. ; Heise, H.FZJ* ; Kuwata, K. ; Tanaka, M. (Corresponding author)

2018
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/21312  doi:10.1073/pnas.1715483115

Abstract: Self-propagating β-sheet–rich fibrillar protein aggregates, amyloidfibers, are often associated with cellular dysfunction and disease.Distinct amyloid conformations dictate different physiological consequences,such as cellular toxicity. However, the origin of the diversityof amyloid conformation remains unknown. Here, we suggest thataltered conformational equilibrium in natively disordered monomericproteins leads to the adaptation of alternate amyloid conformationsthat have different phenotypic effects. We performed acomprehensive high-resolution structural analysis of Sup35NM, anN-terminal fragment of the Sup35 yeast prion protein, and foundthat monomeric Sup35NM harbored latent local compact structuresdespite its overall disordered conformation. When the hidden localmicrostructures were relaxed by genetic mutations or solvent conditions,Sup35NM adopted a strikingly different amyloid conformation,which redirected chaperone-mediated fiber fragmentation and modulatedprion strain phenotypes. Thus, dynamic conformational fluctuationsin natively disordered monomeric proteins represent aposttranslational mechanism for diversification of aggregate structuresand cellular phenotypes.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2018

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; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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