LARGE1 processively polymerizes length-controlled matriglycan on prodystroglycan.

ABSTRACT: Matriglycan is a linear glycan (xylose-β1,3-glucuronate)_n, which binds proteins in the extracellular matrix that contain laminin-globular domains and Lassa Fever Virus. It is indispensable for neuromuscular function. Matriglycan of insufficient length can cause muscular dystrophy with abnormal brain and eye development. LARGE1 (Like-acetylglucosaminyltransferase-1) uniquely synthesizes matriglycan on dystroglycan. The mechanism of matriglycan synthesis is not obvious from cryo-EM reconstructions of LARGE1. However, by reconstituting activity in vitro on recombinant prodystroglycan we show that the presence of the dystroglycan N-terminal domain (DGN), phosphorylated core M3, and a xylose-glucuronate primer are necessary for matriglycan polymerization by LARGE1. By introducing act

SUBMITTER: Joseph S 

PROVIDER: S-EPMC12514197 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature