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J Biol Chem. 2012 May 4;287(19):15317-29. doi: 10.1074/jbc.M111.312587. Epub 2012 Mar 13.

Tight complex formation between Cosmc chaperone and its specific client non-native T-synthase leads to enzyme activity and client-driven dissociation.

Author information

  • 1Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract

The interaction of the endoplasmic reticulum molecular chaperone Cosmc with its specific client T-synthase (Core 1 β1-3-galactosyltransferase) is required for folding of the enzyme and eventual movement of the T-synthase to the Golgi, but the mechanism of interaction is unclear. Here we show that the lumenal domain of recombinant Cosmc directly interacts specifically in either free form or covalently bound to solid supports with denatured T-synthase but not with the active dimeric form of the enzyme. This leads to formation of a relatively stable complex of Cosmc and denatured T-synthase accompanied by formation of reactivated enzyme in an ATP-independent fashion that is not regulated by redox, calcium, pH, or intermolecular disulfide bond formation. The partly refolded and active T-synthase remains tightly bound noncovalently to Cosmc. Dissociation of T-synthase from the complex is promoted by further interactions of the complex with free forms of either native or non-native T-synthase. Taken together, these results demonstrate a novel mechanism in which Cosmc cycles to bind non-native T-synthase, leading to enzyme activity and release in a client-driven process.

PMID:
22416136
[PubMed - indexed for MEDLINE]
PMCID:
PMC3346102
Free PMC Article

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