Do chaperonins boost protein yields by accelerating folding or preventing aggregation?

Biophysical Journal
A I Jewett, J-E Shea

Abstract

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.

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Citations

Nov 19, 2013·PLoS Computational Biology·Alex Dickson, Charles L Brooks
Oct 24, 2009·Cellular and Molecular Life Sciences : CMLS·Andrew I Jewett, Joan-Emma Shea
Apr 18, 2012·Cell Reports·Evan T PowersLila M Gierasch
Mar 12, 2013·Biophysical Journal·Wouter Boomsma, Kresten Lindorff-Larsen
Mar 26, 2009·The Journal of Chemical Physics·Lidia Prieto, Antonio Rey
Apr 18, 2008·The EMBO Journal·Yun-Chi TangManajit Hayer-Hartl
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ke ChenBernhard O Palsson
Jun 3, 2021·Physical Chemistry Chemical Physics : PCCP·Avishek KumarMithun Radhakrishna

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