Species-specific disordered regions and temperature dependence of bisecting GlcNAc-synthetic enzyme MGAT3
5 affiliations
- 1Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan
- 2Faculty of Science, Niigata University, Niigata, Japan
- 3Univ. Lille, Centre National de la Recherche Scientifique ( CNRS), Unité Mixte de Recherche (UMR) 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France
- 4Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
- 5Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan
Abstract
MGAT3 (GnT-III) is a glycosyltransferase that catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the central β-mannose in N-glycans, generating bisecting GlcNAc. These bisecting GlcNAc-bearing N-glycans are implicated in cancer and Alzheimer’s disease and negatively regulate N-glycan maturation. Although the biological significance of bisecting GlcNAc has been increasingly elucidated in mammals, the structure and regulation of MGAT3 remain unclear. We recently found disordered Loop and Tail regions in human MGAT3 that affect its catalytic activity, suggesting the unique structure and mechanism of action of MGAT3. In this study, we extend our analysis to MGAT3 orthologs from various species, including mammals, reptiles, amphibians, and fish. Sequence comparisons and predicted structure analyses showed that the catalytic domain is conserved, whereas the Loop and Tail regions are highly divergent among species. Enzymatic analyses revealed that MGAT3 orthologs exhibit distinct activities and optimal temperature ranges. In particular, Xenopus MGAT3 displayed lower thermostability than human MGAT3 and showed almost no activity under standard enzyme assay conditions, only being active at low temperature. Deep N-glycomic analysis revealed that bisecting GlcNAc-containing N-glycans were abundantly present in Xenopus brain, suggesting that amphibian MGAT3 generates bisecting GlcNAc under native conditions at low temperature. We further found that zebrafish (Danio rerio) MGAT3 enzymes also have distinct temperature dependence compared with mammalian enzymes. These findings indicate that MGAT3 orthologs possess species-specific structures and temperature dependence, providing insight into the functional diversity and adaptive changes of MGAT3 during vertebrate evolution.
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BibTeX
@article{bao2026speciesspecific,
title = {{Species-specific disordered regions and temperature dependence of bisecting GlcNAc-synthetic enzyme MGAT3}},
author = {Wanxue Bao and Shunji Natsuka and Anne Harduin-Lepers and Masamichi Nagae and Takahiro Yamasaki and Atsushi Iwasawa and Kyoko Matsuzawa and Yasuhiko Kizuka},
journal = {The Journal of Biological Chemistry},
year = {2026},
month = sep,
doi = {10.1016/j.jbc.2026.113604},
url = {https://doi.org/10.1016/j.jbc.2026.113604},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Species-specific disordered regions and temperature dependence of bisecting GlcNAc-synthetic enzyme MGAT3
AU - Wanxue Bao
AU - Shunji Natsuka
AU - Anne Harduin-Lepers
AU - Masamichi Nagae
AU - Takahiro Yamasaki
AU - Atsushi Iwasawa
AU - Kyoko Matsuzawa
AU - Yasuhiko Kizuka
PY - 2026
DA - 2026/09/23
JO - The Journal of Biological Chemistry
DO - 10.1016/j.jbc.2026.113604
UR - https://doi.org/10.1016/j.jbc.2026.113604
AB - MGAT3 (GnT-III) is a glycosyltransferase that catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the central β-mannose in N-glycans, generating bisecting GlcNAc. These bisecting GlcNAc-bearing N-glycans are implicated in cancer and Alzheimer’s disease and negatively regulate N-glycan maturation. Although the biological significance of bisecting GlcNAc has been increasingly elucidated in mammals, the structure and regulation of MGAT3 remain unclear. We recently found disordered Loop and Tail regions in human MGAT3 that affect its catalytic activity, suggesting the unique structure and mechanism of action of MGAT3. In this study, we extend our analysis to MGAT3 orthologs from various species, including mammals, reptiles, amphibians, and fish. Sequence comparisons and predicted structure analyses showed that the catalytic domain is conserved, whereas the Loop and Tail regions are highly divergent among species. Enzymatic analyses revealed that MGAT3 orthologs exhibit distinct activities and optimal temperature ranges. In particular, Xenopus MGAT3 displayed lower thermostability than human MGAT3 and showed almost no activity under standard enzyme assay conditions, only being active at low temperature. Deep N-glycomic analysis revealed that bisecting GlcNAc-containing N-glycans were abundantly present in Xenopus brain, suggesting that amphibian MGAT3 generates bisecting GlcNAc under native conditions at low temperature. We further found that zebrafish (Danio rerio) MGAT3 enzymes also have distinct temperature dependence compared with mammalian enzymes. These findings indicate that MGAT3 orthologs possess species-specific structures and temperature dependence, providing insight into the functional diversity and adaptive changes of MGAT3 during vertebrate evolution.
SN - 0021-9258
SN - 1083-351X
ER -