TY  - JOUR
AU  - Mashaghi, Alireza
AU  - Moayed, Fatemeh
AU  - Koers, Eline J
AU  - Zheng, Yang
AU  - Till, Katharina
AU  - Kramer, Günter
AU  - Mayer, Matthias P
AU  - Tans, Sander J
TI  - Direct observation of Hsp90-induced compaction in a protein chain.
JO  - Cell reports
VL  - 41
IS  - 9
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2022-02969
SP  - 111734 
PY  - 2022
N1  - DKFZ-ZMBH Alliance
AB  - 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.
KW  - CP: Molecular biology (Other)
KW  - HSP90 (Other)
KW  - chaperone (Other)
KW  - conformational heterogeneity (Other)
KW  - optical tweezers (Other)
KW  - protein chain compaction (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36450251
DO  - DOI:10.1016/j.celrep.2022.111734
UR  - https://inrepo02.dkfz.de/record/182844
ER  -