The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70

Autor(es)

Goncalves, Conrado C. ^[1] ; Sharon, Itai ^[2] ; Schmeing, T. Martin ^[2] ; Ramos, I, Carlos H. ; Young, Jason C. ^[1]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 AUG 24 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 17/26131-5 - Chaperoma: estudo da relação entre a estrutura dos seus componentes e a manutenção da proteostase
• Beneficiário: Carlos Henrique Inacio Ramos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/03764-0 - Caracterização do papel do sistema HSP70 e da chaperona HSP22 como um complexo de desagregase em humanos
• Beneficiário: Conrado de Campos Gonçalves
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado