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Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding
Author(s) -
Żwirowski Szymon,
Kłosowska Agnieszka,
Obuchowski Igor,
Nillegoda Nadinath B,
Piróg Artur,
Ziętkiewicz Szymon,
Bukau Bernd,
Mogk Axel,
Liberek Krzysztof
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593378
Subject(s) - biology , heat shock protein , hsp70 , protein aggregation , shock (circulatory) , microbiology and biotechnology , biophysics , biochemistry , medicine , gene
Small heat shock proteins ( sH sps) are an evolutionary conserved class of ATP ‐independent chaperones that protect cells against proteotoxic stress. sH sps form assemblies with aggregation‐prone misfolded proteins, which facilitates subsequent substrate solubilization and refolding by ATP ‐dependent Hsp70 and Hsp100 chaperones. Substrate solubilization requires disruption of sH sp association with trapped misfolded proteins. Here, we unravel a specific interplay between Hsp70 and sH sps at the initial step of the solubilization process. We show that Hsp70 displaces surface‐bound sH sps from sH sp–substrate assemblies. This Hsp70 activity is unique among chaperones and highly sensitive to alterations in Hsp70 concentrations. The Hsp70 activity is reflected in the organization of sH sp–substrate assemblies, including an outer dynamic sH sp shell that is removed by Hsp70 and a stable core comprised mainly of aggregated substrates. Binding of Hsp70 to the sH sp/substrate core protects the core from aggregation and directs sequestered substrates towards refolding pathway. The sH sp/Hsp70 interplay has major impact on protein homeostasis as it sensitizes substrate release towards cellular Hsp70 availability ensuring efficient refolding of damaged proteins under favourable folding conditions.