Structural basis for heparan sulfate co-polymerase action by the EXT1-2 complex.

ABSTRACT: Heparan sulfate (HS) proteoglycans are extended (-GlcAβ1,4GlcNAcα1,4-)_n co-polymers containing decorations of sulfation and epimerization that are linked to cell surface and extracellular matrix proteins. In mammals, HS repeat units are extended by an obligate heterocomplex of two exostosin family members, EXT1 and EXT2, where each protein monomer contains distinct GT47 (GT-B fold) and GT64 (GT-A fold) glycosyltransferase domains. In this study, we generated human EXT1-EXT2 (EXT1-2) as a functional heterocomplex and determined its structure in the presence of bound donor and acceptor substrates. Structural data and enzyme activity of catalytic site mutants demonstrate that only two of the four glycosyltransferase domains are major contributors to co-polymer syntheses: the EXT1 G

SUBMITTER: Li H 

PROVIDER: S-EPMC10160006 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature