The Endoplasmic Reticulum Chaperone Cosmc Directly Promotes in Vitro Folding of T-synthase

• Type of Material: Article
• Authors: Rajindra P. Aryal, Emory University; Tongzhong Ju, Emory University; Richard D. Cummings, Emory University
• Language: English
• Date: 2010-01-22
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://www.jbc.org/content/285/4/2456
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 285
• Issue: 4
• Start Page: 2456
• End Page: 2462
• Grant/Funding Information: National Institutes of Health Grant R01 GM068559 (to R. D. C.)
• Keywords: Cosmc; Endoplasmic Reticulum; Galactosyltransferase; T-synthase; Molecular Chaperone; Chaperones/Protein Folding
• Research Categories: Health Sciences, General; Chemistry, Biochemistry

Abstract

The T-synthase is the key β3-galactosyltransferase essential for biosynthesis of core 1 O-glycans (Galβ1–3GalNAcα1-Ser/Thr) in animal cell glycoproteins. Here we describe the novel ability of an endoplasmic reticulum-localized molecular chaperone termed Cosmc to specifically interact with partly denatured T-synthase in vitro to cause partial restoration of activity. By contrast, a mutated form of Cosmc observed in patients with Tn syndrome has reduced chaperone function. The chaperone activity of Cosmc is specific, does not require ATP in vitro, and is effective toward T-synthase but not another β-galactosyltransferase. Cosmc represents the first ER chaperone identified to be required for folding of a glycosyltransferase.