Direct observation of Hsp90-induced compaction in a protein chain

Direct observation of Hsp90-induced compaction in a protein chain

Mashaghi, Alireza (AMOLF; Universiteit Leiden)
Moayed, Fatemeh (ASML; AMOLF)
Koers, Eline J. (University of Nottingham; AMOLF; University of Birmingham)
Zheng, Yang (University Heidelberg)
Till, K. (AMOLF)
Kramer, Günter (German Cancer Research Center; University Heidelberg)
Mayer, Matthias P. (German Cancer Research Center)
Tans, S.J. (TU Delft BN/Sander Tans Lab; AMOLF; Kavli institute of nanoscience Delft)

2022

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.

chaperone
conformational heterogeneity
CP: Molecular biology
HSP90
optical tweezers
protein chain compaction

http://resolver.tudelft.nl/uuid:01777fca-72e6-4d81-94fd-214ed02b40d9

https://doi.org/10.1016/j.celrep.2022.111734

2211-1247

Cell Reports, 41 (9)

Institutional Repository

journal article

© 2022 Alireza Mashaghi, Fatemeh Moayed, Eline J. Koers, Yang Zheng, K. Till, Günter Kramer, Matthias P. Mayer, S.J. Tans