Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan

Molecular & Cellular Proteomics Volume 18 Issue 10 Page 2044-2057 published_at 2019-08-02
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Title ( eng )
Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan
Creator
Mishra Sushil K.
Tokoro Yuko
Sato Keiko
Nakajima Kazuki
Yamaguchi Yoshiki
Taniguchi Naoyuki
Kizuka Yasuhiko
Source Title
Molecular & Cellular Proteomics
Volume 18
Issue 10
Start Page 2044
End Page 2057
Abstract
Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.
Keywords
Glycomics
glycoprotein pathways
glycosylation
glycoproteins
glycoprotein structure
glycoproteomics
bisecting GlcNAc
fucosylation
GnT-III
HNK-1
sialylation
Descriptions
This work was supported by Grant-in-Aid for Scientific Research (C) to Y.K. [17K07356], Leading Initiative for Excellent Young Researchers (LEADER) project to Y.K. from the Japan Society for the Promotion of Science (JSPS), by Takeda Science Foundation, and by Mochida Memorial Foundation for Medical and Pharmaceutical Research.
Language
eng
Resource Type journal article
Publisher
American Society for Biochemistry and Molecular Biology
Date of Issued 2019-08-02
Rights
This research was originally published in Molecular & Cellular Proteomics. Miyako Nakano, Sushil K. Mishra, Yuko Tokoro, Keiko Sato, Kazuki Nakajima, Yoshiki Yamaguchi, Naoyuki Taniguchi, Yasuhiko Kizuka. Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan. Mol Cell Proteomics. 2019; Vol 18: pp2044-pp2057. © the American Society for Biochemistry and Molecular Biology
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認、ご利用ください。
Publish Type Author’s Original
Access Rights open access
Source Identifier
[DOI] 10.1074/mcp.RA119.001534
[ISSN] 1535-9476
[ISSN] 1535-9484
[DOI] https://doi.org/10.1074/mcp.RA119.001534