Crystal structure of the human mitochondrial chaperonin symmetrical football complex

Abstract

Human mitochondria harbor a single type I chaperonin system that is generally thought to function via a unique single-ring intermediate. To date, no crystal structure has been published for any mammalian type I chaperonin complex. In this study, we describe the crystal structure of a football-shaped, double-ring human mitochondrial chaperonin complex at 3.15 Å, which is a novel intermediate, likely representing the complex in an early stage of dissociation. Interestingly, the mitochondrial chaperonin was captured in a state that exhibits subunit asymmetry within the rings and nucleotide symmetry between the rings. Moreover, the chaperonin tetradecamers show a different interring subunit arrangement when compared to GroEL. Our findings suggest that the mitochondrial chaperonins use a mechanism that is distinct from the mechanism of the well-studied Escherichia coli system. mitochondrial chaperonin | symmetrical complex | Hsp60 | chaperone | Hsp10

Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin

“…Chaperonin dissociation into single rings has been previously reported with the mitochondrial hsp60/10 chaperonin and in groEL mutants that dissociate into single rings (Chen et al, 2006; Nielsen et al, 1999; Nisemblat et al, 2015). It has been previously reported that the human mitochondrial chaperonin exists in dynamic equilibrium between single and double rings (Nisemblat et al, 2015).…”

“…It has been previously reported that the human mitochondrial chaperonin exists in dynamic equilibrium between single and double rings (Nisemblat et al, 2015). Bioinformatics analysis suggests that the ring dissociation in the mitochondrial chaperonin is likely due to mutations in the residues that are associated with inter-ring salt bridge contacts.…”

Dynamic Complexes in the Chaperonin-Mediated Protein Folding Cycle

“…Additional evidence for a unique mechanism can be gleaned from the recent crystal structure of a mitochondrial Hsp60 variant in complex with Hsp10, which crystallized as a football complex that displays one subunit in a different conformation than the other six in the ring (Nisemblat et al, 2015). This is in stark contrast to GroEL, for which one hallmark of its mechanism is the high level of cooperativity between subunits in each ring, which results in their concerted movement (Saibil et al, 2013).…”

Disease-Associated Mutations in the HSPD1 Gene Encoding the Large Subunit of the Mitochondrial HSP60/HSP10 Chaperonin Complex

“…Like its bacterial and chloroplast homologs the mitochondrial HSP60/HSP10 complex is composed of two seven-meric rings of the large subunit (HSP60) stacked back to back (Nisemblat et al, 2015; Figure 1A). The HSP60 ring structures enclose an inner cavity that is sealed by lids formed by seven-meric rings of the small subunit (HSP10).…”