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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70

Full text
Author(s):
Goncalves, Conrado C. [1] ; Sharon, Itai [2] ; Schmeing, T. Martin [2] ; Ramos, I, Carlos H. ; Young, Jason C. [1]
Total Authors: 5
Affiliation:
[1] McGill Univ, Dept Biochem, 3655 Promenade Sir William Osler, Room 900, Montreal, PQ H3G 1Y6 - Canada
[2] McGill Univ, Dept Biochem, 3649 Promenade Sir William Osler, Room 457, Montreal, PQ H3G 0B1 - Canada
Total Affiliations: 2
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 11, n. 1 AUG 24 2021.
Web of Science Citations: 0
Abstract

In human cells under stress conditions, misfolded polypeptides can form potentially cytotoxic insoluble aggregates. To eliminate aggregates, the HSP70 chaperone machinery extracts and resolubilizes polypeptides for triage to refolding or degradation. Yeast and bacterial chaperones of the small heat-shock protein (sHSP) family can bind substrates at early stages of misfolding, during the aggregation process. The co-aggregated sHSPs then facilitate downstream disaggregation by HSP70. Because it is unknown whether a human sHSP has this activity, we investigated the disaggregation role of human HSPB1. HSPB1 co-aggregated with unfolded protein substrates, firefly luciferase and mammalian lactate dehydrogenase. The co-aggregates formed with HSPB1 were smaller and more regularly shaped than those formed in its absence. Importantly, co-aggregation promoted the efficient disaggregation and refolding of the substrates, led by HSP70. HSPB1 itself was also extracted during disaggregation, and its homo-oligomerization ability was not required. Therefore, we propose that a human sHSP is an integral part of the chaperone network for protein disaggregation. (AU)

FAPESP's process: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis
Grantee:Carlos Henrique Inacio Ramos
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/03764-0 - Characterization of the role of HSP70 system and HSP22 chaperone as a disaggregase complex in humans
Grantee:Conrado de Campos Gonçalves
Support Opportunities: Scholarships abroad - Research Internship - Doctorate