Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Human mitochondrial chaperonin mHsp60 is vital for mitochondrial protein folding.
• Unlike bacterial GroEL, mHsp60 forms an unstable heptameric ring that readily dissociates.
• This inherent structural dynamics is key to mHsp60's unique function.

Purpose of the Study:

• To elucidate the structural basis for the dynamic nature of the mHsp60 heptamer.
• To understand the mechanism of mHsp10's stabilizing effect on mHsp60.

Main Methods:

• Purification of active heptameric mHsp60.
• Determination of the cryo-electron microscopy (cryo-EM) structure of the mHsp60 heptamer at 3.4 Å resolution.
• Comparative structural analysis of mHsp60 with GroEL and the mHsp60-mHsp10 complex.

Main Results:

• The cryo-EM structure reveals that equatorial domains drive inter-subunit interactions via a four-stranded β sheet.
• Unique sequences in mHsp60 disrupt these interactions, leading to a smaller interface and increased dynamics compared to GroEL.
• mHsp10 binding restores the β sheet and significantly increases the mHsp60 inter-subunit interface, stabilizing the quaternary structure.

Conclusions:

• The study provides structural insights into the inherent dynamics of the mHsp60 heptamer.
• Conserved unique sequences in eukaryotic mHsp60 suggest the importance of structural dynamics.
• The findings clarify the structural mechanism by which mHsp10 stabilizes mHsp60 association, crucial for mitochondrial health.