TY  - JOUR
AU  - Ohhashi, Yumiko
AU  - Yamaguchi, Yoshiki
AU  - Kurahashi, Hiroshi
AU  - Kamatari, Yuji O.
AU  - Sugiyama, Shinju
AU  - Uluca, Boran
AU  - Piechatzek, Timo
AU  - Komi, Yusuke
AU  - Shida, Toshinobu
AU  - Müller, Henrik
AU  - Hanashima, Shinya
AU  - Heise, Henrike
AU  - Kuwata, Kazuo
AU  - Tanaka, Motomasa
TI  - Molecular basis for diversification of yeast prion strain conformation
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 115
IS  - 10
SN  - 1091-6490
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - FZJ-2018-07282
SP  - 2389 - 2394
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29467288
UR  - <Go to ISI:>//WOS:000426671900066
DO  - DOI:10.1073/pnas.1715483115
UR  - https://juser.fz-juelich.de/record/858396
ER  -