4DRV

Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen

4DRV の概要

• エントリーDOI: 10.2210/pdb4drv/pdb
• 関連するPDBエントリー: 4DRR 4DS0
• 分子名称: Outer capsid protein VP4, alpha-L-fucopyranose-(1-2)-[2-acetamido-2-deoxy-alpha-D-galactopyranose-(1-3)]alpha-D-galactopyranose (3 entities in total)
• 機能のキーワード: otavirus, viral protein, cell attachment factor, histo blood group antigen, galectin-fold
• 由来する生物種: Rotavirus sp.
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19097.11

構造登録者

Hu, L.,Crawford, S.E.,Czako, R.,Cortes-Penfield, N.W.,Smith, D.F.,Le Pendu, J.,Estes, M.K.,Prasad, B.V.V. (登録日: 2012-02-17, 公開日: 2012-04-11, 最終更新日: 2023-09-13)

主引用文献

Hu, L.,Crawford, S.E.,Czako, R.,Cortes-Penfield, N.W.,Smith, D.F.,Le Pendu, J.,Estes, M.K.,Prasad, B.V.
Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen.
Nature, 485:256-259, 2012

PubMed Abstract: As with many other viruses, the initial cell attachment of rotaviruses, which are the major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans. The distally located VP8* domain of the rotavirus spike protein VP4 (ref. 5) mediates such interactions. The existing paradigm is that 'sialidase-sensitive' animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas 'sialidase-insensitive' human rotavirus strains bind to glycans with internal Sia such as GM1 (ref. 3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies, it is not yet known how VP8* of human rotaviruses interacts with Sia and whether their cell attachment necessarily involves sialoglycans. Here we show that VP8* of a human rotavirus strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-A-type antibodies as well as significantly enhanced in Chinese hamster ovary cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of human rotavirus. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelia and on red blood cells, and are recognized as susceptibility and cell attachment factors for gastric pathogens like Helicobacter pylori and noroviruses. Our crystallographic studies show that the A-type HBGA binds to the human rotavirus VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific human rotavirus strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world's population.

PubMed: 22504179
DOI: 10.1038/nature10996

実験手法

X-RAY DIFFRACTION (1.56 Å)