Structural basis for client engagement and chaperone cycling by human mitochondrial Hsp60

Abstract

The mitochondrial (mt) molecular chaperone Hsp60 is critical in proteostasis by catalyzing ATP-dependent folding of mitochondrial proteins. In a manner analogous to bacterial GroELS, mtHsp60 is proposed to function by enclosing unfolded ‘client’ proteins in its central chamber, formed in part by its co-chaperone mtHsp10, allowing them to fold without interference from other cellular components. Mutations in mtHsp60 cause severe neurodegenerative diseases termed hereditary spastic paraplegias, and mtHsp60 expression is upregulated in a subset of cancers, making this chaperone a significant therapeutic target.