GroE modulates kinetic partitioning of folding intermediates between alternative states to maximize the yield of biologically active protein

Journal of Molecular Biology
A N Fedorov, T O Baldwin

Abstract

The central issue of chaperone function is the mechanism whereby partitioning of folding polypeptides along the productive pathway may be maximized, while non-productive folding pathways are minimized. We have found that the GroE chaperone is capable of accelerating the rate of the productive pathway of bacterial luciferase alphabeta heterodimer formation. At intermediate temperatures at which the productive pathway and non-productive pathways leading to dimerization-incompetent monomeric forms of the subunits coexist, GroE enhances the yield of native enzyme while minimizing the yield of misfolded protein. These results suggest that GroE releases the subunits in forms capable of achieving the native structure faster than the forms initially bound by the chaperone. At higher temperatures, at which the native enzyme is stable but the dimerization reaction is diminished, GroE is unable to force the productive folding reaction to occur. However, the chaperone decreases the rate of formation of the heterodimerization-incompetent species, thereby enhancing the final yield of active enzyme when the temperature is reduced to the permissive range. Our results suggest a mechanism by which the chaperone functions to maximize the yield of...Continue Reading

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Citations

Oct 27, 2004·Bioscience, Biotechnology, and Biochemistry·Balan VenkateshYoshihiro Ohmiya
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·M W Ribbe, B K Burgess
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Jan 20, 2021·Biochemistry·Eda Koculi, D Thirumalai
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Jul 2, 2021·Frontiers in Molecular Biosciences·Jakub MacošekSebastian Hiller

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