Seminar

Structural bases for the reaction cycle of the human mitochondrial Hsp60-Hsp10 chaperonin complex

Iban Ubarretxena, PhD

The human mitochondrial Hsp60-Hsp10 chaperonin assists the folding of mitochondrial-imported proteins and corrects misfolded polypeptides resulting from mitochondrial stress through a unique reaction cycle that involves alternating single and double mHsp60 rings. The seminar will present the crystal structure of an ATP mimic ground state Hsp60-Hsp10 complex and the cryo-EM structures of the successor (ADP-bound) complex primed for inter-ring split, and the disassembling state (ADP-bound) complex. The structures of these reaction cycle intermediates demonstrate Hsp60-Hsp10 lacks the structural determinants for the inter-ring negative cooperativity observed in GroEL-GroES, and provide evidence for inter-ring split being key for the disassembly of mHsp60-mHsp10 football en route to complete complex dissociation and the release of folded protein substrate.