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Chaperonin-catalyzed rescue of kinetically trapped states in protein folding.
Cell. 2010 Jul 09; 142(1):112-22.Cell

Abstract

GroEL and GroES form a chaperonin nano-cage for single protein molecules to fold in isolation. The folding properties that render a protein chaperonin dependent are not yet understood. Here, we address this question using a double mutant of the maltose-binding protein DM-MBP as a substrate. Upon spontaneous refolding, DM-MBP populates a kinetically trapped intermediate that is collapsed but structurally disordered. Introducing two long-range disulfide bonds into DM-MBP reduces the entropic folding barrier of this intermediate and strongly accelerates native state formation. Strikingly, steric confinement of the protein in the chaperonin cage mimics the kinetic effect of constraining disulfides on folding, in a manner mediated by negative charge clusters in the cage wall. These findings suggest that chaperonin dependence correlates with the tendency of proteins to populate entropically stabilized folding intermediates. The capacity to rescue proteins from such folding traps may explain the uniquely essential role of chaperonin cages within the cellular chaperone network.

Links

Publisher Full Text
linkinghub.elsevier.com
linkinghub.elsevier.com

Authors+Show Affiliations

Chakraborty K
Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Chatila M
No affiliation info available
Sinha J
No affiliation info available
Shi Q
No affiliation info available
Poschner BC
No affiliation info available
Sikor M
No affiliation info available
Jiang G
No affiliation info available
Lamb DC
No affiliation info available
Hartl FU
No affiliation info available
Hayer-Hartl M
No affiliation info available

MeSH

Bacterial ProteinsChaperonin 10Chaperonin 60Escherichia coliEscherichia coli ProteinsMaltose-Binding ProteinsModels, MolecularPeriplasmic Binding ProteinsProtein FoldingRhodospirillum rubrumSpectrometry, FluorescenceThermodynamics

Pub Type(s)

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

Language

eng

PubMed ID

20603018

Citation

Chakraborty, Kausik, et al. "Chaperonin-catalyzed Rescue of Kinetically Trapped States in Protein Folding." Cell, vol. 142, no. 1, 2010, pp. 112-22.
Chakraborty K, Chatila M, Sinha J, et al. Chaperonin-catalyzed rescue of kinetically trapped states in protein folding. Cell. 2010;142(1):112-22.
Chakraborty, K., Chatila, M., Sinha, J., Shi, Q., Poschner, B. C., Sikor, M., Jiang, G., Lamb, D. C., Hartl, F. U., & Hayer-Hartl, M. (2010). Chaperonin-catalyzed rescue of kinetically trapped states in protein folding. Cell, 142(1), 112-22. https://doi.org/10.1016/j.cell.2010.05.027
Chakraborty K, et al. Chaperonin-catalyzed Rescue of Kinetically Trapped States in Protein Folding. Cell. 2010 Jul 9;142(1):112-22. PubMed PMID: 20603018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chaperonin-catalyzed rescue of kinetically trapped states in protein folding. AU - Chakraborty,Kausik, AU - Chatila,Manal, AU - Sinha,Jyoti, AU - Shi,Qiaoyun, AU - Poschner,Bernhard C, AU - Sikor,Martin, AU - Jiang,Guoxin, AU - Lamb,Don C, AU - Hartl,F Ulrich, AU - Hayer-Hartl,Manajit, PY - 2009/11/30/received PY - 2010/03/21/revised PY - 2010/04/23/accepted PY - 2010/7/7/entrez PY - 2010/7/7/pubmed PY - 2010/8/3/medline SP - 112 EP - 22 JF - Cell JO - Cell VL - 142 IS - 1 N2 - GroEL and GroES form a chaperonin nano-cage for single protein molecules to fold in isolation. The folding properties that render a protein chaperonin dependent are not yet understood. Here, we address this question using a double mutant of the maltose-binding protein DM-MBP as a substrate. Upon spontaneous refolding, DM-MBP populates a kinetically trapped intermediate that is collapsed but structurally disordered. Introducing two long-range disulfide bonds into DM-MBP reduces the entropic folding barrier of this intermediate and strongly accelerates native state formation. Strikingly, steric confinement of the protein in the chaperonin cage mimics the kinetic effect of constraining disulfides on folding, in a manner mediated by negative charge clusters in the cage wall. These findings suggest that chaperonin dependence correlates with the tendency of proteins to populate entropically stabilized folding intermediates. The capacity to rescue proteins from such folding traps may explain the uniquely essential role of chaperonin cages within the cellular chaperone network. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/20603018/Chaperonin_catalyzed_rescue_of_kinetically_trapped_states_in_protein_folding_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(10)00563-5 DB - PRIME DP - Unbound Medicine ER -