7vmt

Publication Abstract from PubMed

N-Glycosylation is a common post-translational modification, and the number of GlcNAc branches in N-glycans impacts glycoprotein functions. N-Acetylglucosaminyltransferase-IVa (GnT-IVa, also designated as MGAT4A) forms a beta1-4 GlcNAc branch on the alpha1-3 mannose arm in N-glycans. Downregulation or loss of GnT-IVa causes diabetic phenotypes by dysregulating glucose transporter-2 in pancreatic beta-cells. Despite the physiological importance of GnT-IVa, its structure and catalytic mechanism are poorly understood. Here, we identify the lectin domain in mouse GnT-IVa's C-terminal region. The crystal structure of the lectin domain shows structural similarity to a bacterial GlcNAc-binding lectin. Comprehensive glycan binding assay using 157 glycans and solution NMR reveal that the GnT-IVa lectin domain selectively interacts with the product N-glycans having a beta1-4 GlcNAc branch. Point mutation of the residue critical to sugar recognition impairs the enzymatic activity, suggesting that the lectin domain is a regulatory subunit for efficient catalytic reaction. Our findings provide insights into how branching structures of N-glycans are biosynthesized.

Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A).,Nagae M, Hirata T, Tateno H, Mishra SK, Manabe N, Osada N, Tokoro Y, Yamaguchi Y, Doerksen RJ, Shimizu T, Kizuka Y Commun Biol. 2022 Jul 19;5(1):695. doi: 10.1038/s42003-022-03661-w. PMID:35854001^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.