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@ARTICLE{Mashaghi:182844,
author = {A. Mashaghi and F. Moayed and E. J. Koers and Y. Zheng and
K. Till and G. Kramer$^*$ and M. P. Mayer and S. J. Tans},
title = {{D}irect observation of {H}sp90-induced compaction in a
protein chain.},
journal = {Cell reports},
volume = {41},
number = {9},
issn = {2211-1247},
address = {[New York, NY]},
publisher = {Elsevier},
reportid = {DKFZ-2022-02969},
pages = {111734},
year = {2022},
note = {DKFZ-ZMBH Alliance},
abstract = {The chaperone heat shock protein 90 (Hsp90) is well known
to undergo important conformational changes, which depend on
nucleotide and substrate interactions. Conversely, how the
conformations of its unstable and disordered substrates are
affected by Hsp90 is difficult to address experimentally yet
is central to its function. Here, using optical tweezers, we
find that Hsp90 promotes local contractions in unfolded
chains that drive their global compaction down to dimensions
of folded states. This compaction has a gradual nature while
showing small steps, is stimulated by ATP, and performs
mechanical work against counteracting forces that expand the
chain dimensions. The Hsp90 interactions suppress the
formation of larger-scale folded, misfolded, and aggregated
structures. The observations support a model in which Hsp90
alters client conformations directly by promoting local
intra-chain interactions while suppressing distant ones. We
conjecture that chain compaction may be central to how Hsp90
protects unstable clients and cooperates with Hsp70.},
keywords = {CP: Molecular biology (Other) / HSP90 (Other) / chaperone
(Other) / conformational heterogeneity (Other) / optical
tweezers (Other) / protein chain compaction (Other)},
cin = {A250},
ddc = {610},
cid = {I:(DE-He78)A250-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36450251},
doi = {10.1016/j.celrep.2022.111734},
url = {https://inrepo02.dkfz.de/record/182844},
}