6JYN

GII.13/21 noroviruses recognize glycans with a terminal beta-galactose via an unconventional glycan binding site

6JYN の概要

• エントリーDOI: 10.2210/pdb6jyn/pdb
• 分子名称: human norovirus P domain protein, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: human noroviruses, viral protein
• 由来する生物種: Human norovirus - Alphatron
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136972.15

構造登録者

Duan, Z.,Xin, C. (登録日: 2019-04-26, 公開日: 2019-05-22, 最終更新日: 2024-03-27)

主引用文献

Cong, X.,Sun, X.M.,Qi, J.X.,Li, H.B.,Chai, W.G.,Zhang, Q.,Wang, H.,Kong, X.Y.,Song, J.,Pang, L.L.,Jin, M.,Li, D.D.,Tan, M.,Duan, Z.J.
GII.13/21 Noroviruses Recognize Glycans with a Terminal beta-Galactose via an Unconventional Glycan Binding Site.
J.Virol., 93:-, 2019

PubMed Abstract: Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as host susceptibility factors. GII.13 and GII.21 huNoVs form a unique genetic lineage that emerged from mainstream GII NoVs via development of a new, nonconventional glycan binding site (GBS) that binds Le antigen. This previous finding raised the question of whether the new GII.13/21 GBS really has such a narrow glycan binding spectrum. In this study, we provide solid phenotypic and structural evidence indicating that this new GBS recognizes a group of glycans with a common terminal β-galactose (β-Gal). First, we found that P domain proteins of GII.13/21 huNoVs circulating at different times bound three glycans sharing a common terminal β-Gal, including Lec, lactose, and mucin core 2. Second, we solved the crystal structures of the GII.13 P dimers in complex with Lec and mucin core 2, which showed that β-Gal is the major binding saccharide. Third, nonfat milk and lactose blocked the GII.13/21 P domain-glycan binding, which may explain the low prevalence of GII.13/21 viruses. Our data provide new insight into the host interactions and epidemiology of huNoVs, which would help in the control and prevention of NoV-associated diseases. Evidence from both phenotypic binding assay and structural study support the observed interactions of human noroviruses (huNoVs) with histo-blood group antigens (HBGAs) as receptors or attachment factors, affecting their host susceptibility. GII.13 and GII.21 genotypes form a unique genetic lineage that differs from the mainstream GII huNoVs in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Le antigen, we found in this study that they can interact with a group of glycans with a common terminal β-Gal, including Lec, lactose, and mucin core 2. However, this wide glycan binding spectrum in a unique binding mode of the GII.13/21 huNoVs appears not to increase their prevalence, probably due to the existence of decoy glycan receptors in human gastrointestinal tract limiting their infection. Our findings shed light on the host interaction and epidemiology of huNoVs, which would impact the strategy of huNoV control and prevention.

PubMed: 31118252
DOI: 10.1128/JVI.00723-19

実験手法

X-RAY DIFFRACTION (1.599 Å)