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  Folding of large multidomain proteins by partial encapsulation in the chaperonin TRiC/CCT

Rüßmann, F., Stemp, M. J., Mönkemeyer, L., Etchells, S. A., Bracher, A., & Hartl, F.-U. (2012). Folding of large multidomain proteins by partial encapsulation in the chaperonin TRiC/CCT. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(52), 21208-21215. doi:10.1073/pnas.1218836109.

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 Creators:
Rüßmann, Florian1, Author           
Stemp, Markus Johann1, Author           
Mönkemeyer, Leonie1, Author           
Etchells, Stephanie A.1, Author           
Bracher, Andreas1, Author           
Hartl, Franz-Ulrich1, Author           
Affiliations:
1Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              

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Free keywords: GROUP-II CHAPERONIN; CRYO-EM STRUCTURE; FUNCTION IN-VIVO; EUKARYOTIC CHAPERONIN; CYTOPLASMIC CHAPERONIN; MOLECULAR CHAPERONES; CRYSTAL-STRUCTURE; CONFORMATIONAL-CHANGES; RIBOSOMAL TRANSLOCASE; BINDING-SITESfolding cage; molecular chaperone; Snu114 homolog; 116 kDa U5 small nuclear ribonucleoprotein component;
 Abstract: The eukaryotic chaperonin, TRiC/CCT (TRiC, TCP-1 ring complex; CCT, chaperonin containing TCP-1), uses a built-in lid to mediate protein folding in an enclosed central cavity. Recent structural data suggest an effective size limit for the TRiC folding chamber of similar to 70 kDa, but numerous chaperonin substrates are substantially larger. Using artificial fusion constructs with actin, an obligate chaperonin substrate, we show that TRiC can mediate folding of large proteins by segmental or domain-wise encapsulation. Single or multiple protein domains up to similar to 70 kDa are stably enclosed by stabilizing the ATP-hydrolysis transition state of TRiC. Additional domains, connected by flexible linkers that pass through the central opening of the folding chamber, are excluded and remain accessible to externally added protease. Experiments with the physiological TRiC substrate hSnu114, a 109-kDa multidomain protein, suggest that TRiC has the ability to recognize domain boundaries in partially folded intermediates. In the case of hSnu114, this allows the selective encapsulation of the C-terminal similar to 45-kDa domain and segments thereof, presumably reflecting a stepwise folding mechanism. The capacity of the eukaryotic chaperonin to overcome the size limitation of the folding chamber may have facilitated the explosive expansion of the multidomain proteome in eukaryotes.

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Language(s): eng - English
 Dates: 2012-12-26
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000313627700025
DOI: 10.1073/pnas.1218836109
 Degree: -

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Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Source Genre: Journal
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Publ. Info: 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA : NATL ACAD SCIENCES
Pages: - Volume / Issue: 109 (52) Sequence Number: - Start / End Page: 21208 - 21215 Identifier: ISSN: 0027-8424