A structural approach for unraveling the mechanism of function of the human mitochondrial Hsp60-Hsp10 complex

Type Ι Hsp60 family is essential for the viability of almost all organisms from bacteria and yeast to humans. Hsp60 assemble into tetradecameric double-ring structures and assist folding of newly translated, stress denatured and translocated proteins, in an ATP-dependent manner, by sequestering them in the inner cavity of their barrel structure, and their function, in contrary to type ΙΙ family, depends on cooperation with co-chaperonin protein, Hsp10. In mitochondria, they mediate the folding of matrix localized proteins but also was reported to be implicated in a wide range of extra-mitochondrial activities. Despite the high homology among type Ι Hsp60s, recent studies point to unique structural and functional properties of the mammalian mitochondrial chaperonin system, implying a unique mode of action distinct of that known from the extensively studied bacterial GroES-GroEL system. In this study, I describe three structures of the human WT Hsp60-Hsp10 complex using both crystallography and cryo EM at resolutions ranging from 3.8 to 3.1 Å, representing different stage intermediates.