Print Email Facebook Twitter Direct observation of Hsp90-induced compaction in a protein chain Title Direct observation of Hsp90-induced compaction in a protein chain Author 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) Date 2022 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. Subject chaperoneconformational heterogeneityCP: Molecular biologyHSP90optical tweezersprotein chain compaction To reference this document use: http://resolver.tudelft.nl/uuid:01777fca-72e6-4d81-94fd-214ed02b40d9 DOI https://doi.org/10.1016/j.celrep.2022.111734 ISSN 2211-1247 Source Cell Reports, 41 (9) Part of collection Institutional Repository Document type journal article Rights © 2022 Alireza Mashaghi, Fatemeh Moayed, Eline J. Koers, Yang Zheng, K. Till, Günter Kramer, Matthias P. Mayer, S.J. Tans Files PDF 1_s2.0_S2211124722016126_main.pdf 2.14 MB Close viewer /islandora/object/uuid:01777fca-72e6-4d81-94fd-214ed02b40d9/datastream/OBJ/view