BIOPHYSICAL THEORY AND MODELING |
Do chaperonins boost protein yields by accelerating
folding or preventing aggregation?
Andrew Iain Jewett 1 and Joan-Emma Shea 1*
1 U. C. Santa Barbara
* To whom correspondence should be addressed. E-mail: shea{at}chem.ucsb.edu.
Submitted on June 18, 2007
Revised on September 13, 2007
Accepted on 4 December 2007
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Abstract |
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The GroEL chaperonin has the ability to behave as an "unfoldase", repeatedly denaturing proteins upon binding, which in turn frees them from kinetic traps and increases their folding rates. The complex formed by GroEL+GroES+ATP can also act as a "infinite dilution cage", enclosing proteins within a protective container where they can fold without danger of aggregation. Controversy remains over which of these two properties is more critical to the GroEL/ES chaperonin's function. We probe the importance of the "unfoldase" nature of GroEL under conditions where aggregation is the predominant protein degradation pathway. We consider the effect of a hypothetical mutation to GroEL which increases the cycle frequency of GroEL/ES by increasing the rate of hydrolysis of GroEL-bound ATP. Using a simple kinetic model, we show that this modified chaperonin would be self-defeating: any potential reduction in folding time would be negated by an increase in time spent in the bulk, causing an increase in aggregation and a net decrease in protein folding yields.
Key Words:
aggregation, chaperonin, kinetics, protein, theory
