Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides

Smriti Priya, Sandeep K. Sharma, Pierre Goloubinoff*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Stress-denatured or de novo synthesized and translocated unfolded polypeptides can spontaneously reach their native state without assistance of other proteins. Yet, the pathway to native folding is complex, stress-sensitive and prone to errors. Toxic misfolded and aggregated conformers may accumulate in cells and lead to degenerative diseases. Members of the canonical conserved families of molecular chaperones, Hsp100s, Hsp70/110/40s, Hsp60/CCTs, the small Hsps and probably also Hsp90s, can recognize and bind with high affinity, abnormally exposed hydrophobic surfaces on misfolded and aggregated polypeptides. Binding to Hsp100, Hsp70, Hsp110, Hsp40, Hsp60, CCTs and Trigger factor may cause partial unfolding of the misfolded polypeptide substrates, and ATP hydrolysis can induce further unfolding and release from the chaperone, leading to spontaneous refolding into native proteins with low-affinity for the chaperones. Hence, specific chaperones act as catalytic polypeptide unfolding isomerases, rerouting cytotoxic misfolded and aggregated polypeptides back onto their physiological native refolding pathway, thus averting the onset of protein conformational diseases.

Original languageEnglish
Pages (from-to)1981-1987
Number of pages7
JournalFEBS Letters
Issue number13
StatePublished - 27 Jun 2013
Externally publishedYes


  • Protein aggregation Conformational diseases Heat shock proteins Chaperonins Isomerase


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