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Identification of a redox‐regulated chaperone network
Author(s) -
Hoffmann Jörg H,
Linke Katrin,
Graf Paul CF,
Lilie Hauke,
Jakob Ursula
Publication year - 2004
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 - 10.1038/sj.emboj.7600016
Subject(s) - chaperone (clinical) , groel , foldase , protein folding , biology , groes , biophysics , biochemistry , heat shock protein , protein structure , microbiology and biotechnology , escherichia coli , medicine , pathology , gene
We have identified and reconstituted a multicomponent redox‐chaperone network that appears to be designed to protect proteins against stress‐induced unfolding and to refold proteins when conditions return to normal. The central player is Hsp33, a redox‐regulated molecular chaperone. Hsp33, which is activated by disulfide bond formation and subsequent dimerization, works as an efficient chaperone holdase that binds to unfolding protein intermediates and maintains them in a folding competent conformation. Reduction of Hsp33 is catalyzed by the glutaredoxin and thioredoxin systems in vivo , and leads to the formation of highly active, reduced Hsp33 dimers. Reduction of Hsp33 is necessary but not sufficient for substrate protein release. Substrate dissociation from Hsp33 is linked to the presence of the DnaK/DnaJ/GrpE foldase system, which alone, or in concert with the GroEL/GroES system, then supports the refolding of the substrate proteins. Upon substrate release, reduced Hsp33 dimers dissociate into inactive monomers. This regulated substrate transfer ultimately links substrate release and Hsp33 inactivation to the presence of available DnaK/DnaJ/GrpE, and, therefore, to the return of cells to non‐stress conditions.