Matriglycan biosynthesis on DAG1

Matriglycan biosynthesis on DAG1 α-Dystroglycan is a 624 aa product of the dystroglycan (DAG1) gene. As a monomer or a heterodimer with the 324 aa beta-dystroglycan it is a central component of the dystrophin-glycoprotein complex. Most of its properties like laminin binding or arenavirus receptor function (reviewed in Moriguchi & Campbell, 2015; Nickolls & Bönnemann, 2018; Katz & Diskin, 2024) are provided by matriglycan chains that are biosynthesized on threonine residues, in the mucin like domain, positions 317 455, of α-dystroglycan. Matriglycan is a glycosaminoglycan (GAG)-like polysaccharide consisting of a long linear chain of repeating [-3GlcAβ1,3Xylα1-] heterodisaccharide and two ribitolphosphate subunits connected via the trisaccharide linker GalNAc-GlcNAc-ManP (aka Core M3) to O-threonines on α-dystroglycan. At least 19 genes are involved in the biosynthesis of this modification, mutations of which have been shown to lead to α-dystroglycanopathies, rare illnesses ranging from mild muscular dystrophy to severe congenital syndromes that are characterized by progressive muscle weakness, brain abnormalities and seizures, as well as eye problems.