Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A).

Autor: Nagae, Masamichi, Hirata, Tetsuya, Tateno, Hiroaki, Mishra, Sushil K., Manabe, Noriyoshi, Osada, Naoko, Tokoro, Yuko, Yamaguchi, Yoshiki, Doerksen, Robert J., Shimizu, Toshiyuki, Kizuka, Yasuhiko
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Zdroj: Communications Biology; 7/19/2022, Vol. 5 Issue 1, p1-11, 11p
Abstrakt: 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. X-ray crystallography together with NMR and computer modelling shed light on the structure and catalytic mechanism of GnTIVa, a key enzyme involved in GlcNAc branch synthesis, that bears an unusual C-terminal lectin domain that regulates its catalytic activity. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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