Abstract
Posttranslational modification of alpha-dystroglycan (α-DG) by the like-acetylglucosaminyltransferase (LARGE) is required for it to function as an extracellular matrix (ECM) receptor. Mutations in the LARGE gene have been identified in congenital muscular dystrophy patients with brain abnormalities. However, the precise function of LARGE remains unclear. Here we found that LARGE could act as a bifunctional glycosyltransferase, with both xylosyltransferase and glucuronyltransferase activities, which produced repeating units of [-3-xylose-α1,3-glucuronic acid-β1-]. This modification allowed α-DG to bind laminin-G domain-containing ECM ligands.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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CHO Cells
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Carbohydrate Conformation
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Catalytic Domain
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Cricetinae
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Dystroglycans / chemistry
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Dystroglycans / metabolism*
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Glucuronic Acid / metabolism
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Glucuronosyltransferase / metabolism
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Glycosaminoglycans / metabolism
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Glycosylation
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HEK293 Cells
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Humans
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Laminin / metabolism
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Ligands
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Mice
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Mutation
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N-Acetylglucosaminyltransferases / chemistry
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N-Acetylglucosaminyltransferases / genetics
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N-Acetylglucosaminyltransferases / metabolism*
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Pentosyltransferases / metabolism
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Polysaccharides / metabolism*
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Protein Processing, Post-Translational
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Recombinant Proteins / metabolism
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UDP Xylose-Protein Xylosyltransferase
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Xylose / metabolism
Substances
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Glycosaminoglycans
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Laminin
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Ligands
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Polysaccharides
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Recombinant Proteins
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Dystroglycans
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Glucuronic Acid
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Xylose
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LARGE1 protein, human
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Large1 protein, mouse
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N-Acetylglucosaminyltransferases
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Glucuronosyltransferase
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Pentosyltransferases