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The ‘sequential allosteric ring’ mechanism in the eukaryotic chaperonin‐assisted folding of actin and tubulin
Author(s) -
Llorca Oscar,
MartínBenito Jaime,
Grantham Julie,
RitcoVonsovici Monica,
Willison Keith R.,
Carrascosa José L.,
Valpuesta José M.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.15.4065
Subject(s) - chaperonin , tubulin , biology , cytoskeleton , actin , allosteric regulation , microtubule , protein subunit , microbiology and biotechnology , biophysics , chaperone (clinical) , biochemistry , protein folding , enzyme , medicine , pathology , gene , cell
Folding to completion of actin and tubulin in the eukaryotic cytosol requires their interaction with cytosolic chaperonin CCT [chaperonin containing tailless complex polypeptide 1 (TCP‐1)]. Three‐dimensional reconstructions of nucleotide‐free CCT complexed to either actin or tubulin show that CCT stabilizes both cytoskeletal proteins in open and quasi‐folded conformations mediated through interactions that are both subunit specific and geometry dependent. Here we find that upon ATP binding, mimicked by the non‐hydrolysable analog AMP‐PNP (5′‐adenylyl‐imido‐diphosphate), to both CCT–α‐actin and CCT–β‐tubulin complexes, the chaperonin component undergoes concerted movements of the apical domains, resulting in the cavity being closed off by the helical protrusions of the eight apical domains. However, in contrast to the GroE system, generation of this closed state does not induce the release of the substrate into the chaperonin cavity, and both cytoskeletal proteins remain bound to the chaperonin apical domains. Docking of the AMP‐PNP–CCT‐bound conformations of α‐actin and β‐tubulin to their respective native atomic structures suggests that both proteins have progressed towards their native states.