title: The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase.
abstract: The T-synthase is the key beta 3-galactosyltransferase essential for biosynthesis of core 1 O-glycans (Gal beta 1-3GalNAc alpha 1-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 beta-galactosyltransferase. Cosmc represents the first ER chaperone identified to be required for folding of a glycosyltransferase.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Rajindra P
authors.initials: RP
authors.lastname: Aryal
authors.forename: Tongzhong
authors.initials: T
authors.lastname: Ju
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005700:Galactosyltransferases / Q000737:chemistry* / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017350:N-Acetylgalactosaminyltransferases; D009842:Oligopeptides / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D012995:Solubility
chemical_list: D014408:Biomarkers, Tumor; C505369:C1GALT1C1 protein, human; D018832:Molecular Chaperones; D009842:Oligopeptides; D000255:Adenosine Triphosphate; D008156:Luciferases; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase