Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation.

ABSTRACT: Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient cata

SUBMITTER: Lira-Navarrete E 

PROVIDER: S-EPMC4432651 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature