This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.107.113209v1 94/8/2987    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Jewett, A. I. Articles by Shea, J.-E. PubMed PubMed Citation Articles by Jewett, A. I. Articles by Shea, J.-E.

Do Chaperonins Boost Protein Yields by Accelerating Folding or Preventing Aggregation?

Department of Chemistry and Biochemistry, Department of Physics, University of California, Santa Barbara, California

Correspondence: Address reprint requests to J.-E. Shea, E-mail: shea{at}chem.ucsb.edu.

The GroEL chaperonin has the ability to behave as an unfoldase, repeatedly denaturing proteins upon binding, which in turn can free them from kinetic traps and increase their folding rates. The complex formed by GroEL+GroES+ATP can also act as an 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.