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GroEL channels the folding of thioredoxin along one kinetic route.
J Mol Biol. 2001 Dec 14; 314(5):1167-79.JM

Abstract

Many proteins display complex folding kinetics, which represent multiple parallel folding pathways emanating from multiple unfolded forms and converging to the unique native form. The small protein thioredoxin from Escherichia coli is one such protein. The effect of the chaperonin GroEL on modulating the complex energy landscape that separates the unfolded ensemble from the native state of thioredoxin has been studied. It is shown that while the fluorescence change accompanying folding occurs in five kinetic phases in the absence of GroEL, only the two slowest kinetic phases are discernible in the presence of saturating concentrations of GroEL. This result is shown to be consistent with only one out of several available folding routes being operational in the presence of GroEL. It is shown that native protein, which forms via fast as well as slow routes in the absence of GroEL, forms only via a slow route in its presence. The effect of GroEL on the folding of thioredoxin is shown to be the consequence of it binding differentially to the many folding-competent forms. While some of these forms can continue folding when bound to GroEL, others cannot. All molecules are then drawn into the operational folding route by the law of mass action. This observation indicates a new role for GroEL, which is to bias the energy landscape of a folding polypeptide towards fewer available pathways. It is suggested that such channeling might be a mechanism to avoid possible aggregation-prone routes available to a refolding polypeptide in vivo.

Authors+Show Affiliations

National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore 560065, India.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11743732

Citation

Bhutani, N, and J B. Udgaonkar. "GroEL Channels the Folding of Thioredoxin Along One Kinetic Route." Journal of Molecular Biology, vol. 314, no. 5, 2001, pp. 1167-79.
Bhutani N, Udgaonkar JB. GroEL channels the folding of thioredoxin along one kinetic route. J Mol Biol. 2001;314(5):1167-79.
Bhutani, N., & Udgaonkar, J. B. (2001). GroEL channels the folding of thioredoxin along one kinetic route. Journal of Molecular Biology, 314(5), 1167-79.
Bhutani N, Udgaonkar JB. GroEL Channels the Folding of Thioredoxin Along One Kinetic Route. J Mol Biol. 2001 Dec 14;314(5):1167-79. PubMed PMID: 11743732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GroEL channels the folding of thioredoxin along one kinetic route. AU - Bhutani,N, AU - Udgaonkar,J B, PY - 2001/12/18/pubmed PY - 2002/2/7/medline PY - 2001/12/18/entrez SP - 1167 EP - 79 JF - Journal of molecular biology JO - J Mol Biol VL - 314 IS - 5 N2 - Many proteins display complex folding kinetics, which represent multiple parallel folding pathways emanating from multiple unfolded forms and converging to the unique native form. The small protein thioredoxin from Escherichia coli is one such protein. The effect of the chaperonin GroEL on modulating the complex energy landscape that separates the unfolded ensemble from the native state of thioredoxin has been studied. It is shown that while the fluorescence change accompanying folding occurs in five kinetic phases in the absence of GroEL, only the two slowest kinetic phases are discernible in the presence of saturating concentrations of GroEL. This result is shown to be consistent with only one out of several available folding routes being operational in the presence of GroEL. It is shown that native protein, which forms via fast as well as slow routes in the absence of GroEL, forms only via a slow route in its presence. The effect of GroEL on the folding of thioredoxin is shown to be the consequence of it binding differentially to the many folding-competent forms. While some of these forms can continue folding when bound to GroEL, others cannot. All molecules are then drawn into the operational folding route by the law of mass action. This observation indicates a new role for GroEL, which is to bias the energy landscape of a folding polypeptide towards fewer available pathways. It is suggested that such channeling might be a mechanism to avoid possible aggregation-prone routes available to a refolding polypeptide in vivo. SN - 0022-2836 UR - https://www.unboundmedicine.com/medline/citation/11743732/GroEL_channels_the_folding_of_thioredoxin_along_one_kinetic_route_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(00)95193-3 DB - PRIME DP - Unbound Medicine ER -