7VMT

Crystal structure of murine N-acetylglucosaminyl transferase IVa (GnT-IVa) lectin domain in unliganded form

Summary for 7VMT

• Entry DOI: 10.2210/pdb7vmt/pdb
• Descriptor: Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A soluble form, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL (3 entities in total)
• Functional Keywords: glycosyltransferase, lectin, glcnac transferase, posttranslational modification, sugar binding protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 6
• Total formula weight: 99998.10

Authors

Nagae, M. (deposition date: 2021-10-09, release date: 2022-06-15, Last modification date: 2024-05-29)

Primary citation

Nagae, M.,Hirata, T.,Tateno, H.,Mishra, S.K.,Manabe, N.,Osada, N.,Tokoro, Y.,Yamaguchi, Y.,Doerksen, R.J.,Shimizu, T.,Kizuka, Y.
Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A).
Commun Biol, 5:695-695, 2022

PubMed Abstract: 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 β1-4 GlcNAc branch on the α1-3 mannose arm in N-glycans. Downregulation or loss of GnT-IVa causes diabetic phenotypes by dysregulating glucose transporter-2 in pancreatic β-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 β1-4 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.

PubMed: 35854001
DOI: 10.1038/s42003-022-03661-w

Experimental method

X-RAY DIFFRACTION (1.95000641903 Å)