Quasi-native chaperonin-bound intermediates in facilitated protein folding

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• Chaperonins are crucial molecular chaperones that facilitate protein folding.
• Current models propose chaperonins unfold misfolded proteins, releasing them for multiple folding attempts.

Purpose of the Study:

• To investigate the mechanism of action of cytosolic chaperonin (c-cpn) in protein folding.
• To determine if proteins can acquire native-like structure while bound to chaperonins.

Main Methods:

• Studied the interaction of alpha-tubulin with cytosolic chaperonin (c-cpn).
• Investigated the role of cofactors in the chaperonin-assisted folding reaction.
• Analyzed the properties of chaperonin-bound folding intermediates.

Main Results:

• Demonstrated that alpha-tubulin cycling by c-cpn can be separated from cofactor-dependent folding.
• Observed the accumulation of stable, chaperonin-bound folding intermediates.
• Showed these intermediates bind GTP nonexchangeably, indicating quasi-native structure.
• Provided evidence that native-like structure can form without protein release from c-cpn.

Conclusions:

• Challenges prevailing models suggesting chaperonins primarily unfold proteins.
• Suggests chaperonins may allow proteins to attain significant native-like structure while still bound.
• Highlights a potential alternative mechanism for chaperonin-mediated protein folding.