Mutational and functional analysis of Large in a novel CHO glycosylation mutant.

ABSTRACT: Inactivating mutations of Large reduce the functional glycosylation of alpha-dystroglycan (alpha-DG) and lead to muscular dystrophy in mouse and humans. The N-terminal domain of Large is most similar to UDP-glucose glucosyltransferases (UGGT), and the C-terminal domain is related to the human i blood group transferase beta1,3GlcNAcT-1. The amino acids at conserved motifs DQD+1 and DQD+3 in the UGGT domain are necessary for mammalian UGGT activity. When the corresponding residues were mutated to Ala in mouse Large, alpha-DG was not functionally glycosylated. A similar result was obtained when a DXD motif in the beta1,3GlcNAcT-1 domain was mutated to AIA. Therefore, the first putative glycosyltransferase domain of Large has properties of a UGGT and the second of a typical glycosyltransferase

SUBMITTER: Aguilan JT 

PROVIDER: S-EPMC2720279 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature