Direct observation of Hsp90-induced compaction in a protein chain.

Autor:	Mashaghi A; AMOLF, Amsterdam, the Netherlands; Leiden Academic Centre for Drug Research, aculty of Science, Leiden University, Leiden, the Netherlands., Moayed F; AMOLF, Amsterdam, the Netherlands; ASML, Veldhoven, the Netherlands., Koers EJ; AMOLF, Amsterdam, the Netherlands; Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, UK; Division of Physiology, Pharmacology & Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK., Zheng Y; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Till K; AMOLF, Amsterdam, the Netherlands., Kramer G; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany., Mayer MP; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Tans SJ; AMOLF, Amsterdam, the Netherlands; Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands. Electronic address: s.j.tans@tudelft.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Nov 29; Vol. 41 (9), pp. 111734.
DOI:	10.1016/j.celrep.2022.111734
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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