Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network
AUTOR(ES)
Goloubinoff, Pierre
FONTE
The National Academy of Sciences
RESUMO
A major activity of molecular chaperones is to prevent aggregation and refold misfolded proteins. However, when allowed to form, protein aggregates are refolded poorly by most chaperones. We show here that the sequential action of two Escherichia coli chaperone systems, ClpB and DnaK-DnaJ-GrpE, can efficiently solubilize excess amounts of protein aggregates and refold them into active proteins. Measurements of aggregate turbidity, Congo red, and 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid binding, and of the disaggregation/refolding kinetics by using a specific ClpB inhibitor, suggest a mechanism where (i) ClpB directly binds protein aggregates, ATP induces structural changes in ClpB, which (ii) increase hydrophobic exposure of the aggregates and (iii) allow DnaK-DnaJ-GrpE to bind and mediate dissociation and refolding of solubilized polypeptides into native proteins. This efficient mechanism, whereby chaperones can catalytically solubilize and refold a wide variety of large and stable protein aggregates, is a major addition to the molecular arsenal of the cell to cope with protein damage induced by stress or pathological states.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24133Documentos Relacionados
- High pressure fosters protein refolding from aggregates at high concentrations
- A new complement function: solubilization of antigen-antibody aggregates.
- Solubilization and renaturation of overexpressed aggregates of mutant tryptophan synthase alpha-subunits.
- Requirements for the solubilization of immune aggregates by complement. The role of the classical pathway.
- Protein Kinase Activity from Vaccinia Virions: Solubilization and Separation into Heat-Labile and Heat-Stable Components