期刊
EMBO JOURNAL
卷 21, 期 5, 页码 885-897出版社
WILEY
DOI: 10.1093/emboj/21.5.885
关键词
galectin; hemagglutinin; rotavirus; sialic acid; structure
资金
- NCI NIH HHS [CA 13202, R01 CA013202, R37 CA013202] Funding Source: Medline
- NIAID NIH HHS [K08 AI 01496] Funding Source: Medline
- NIGMS NIH HHS [P01 GM047467, GM 47467] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA013202, R37CA013202] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K08AI001496] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P01GM047467] Funding Source: NIH RePORTER
Cell attachment and membrane penetration are functions of the rotavirus outer capsid spike protein, VP4. An activating tryptic cleavage of VP4 produces the N-terminal fragment, VP8*, which is the viral hemagglutinin and an important target of neutralizing antibodies. We have determined, by X-ray crystallography, the atomic structure of the VP8* core bound to sialic acid and, by NMR spectroscopy, the structure of the unliganded VP8* core. The domain has the beta-sandwich fold of the galectins, a family of sugar binding proteins. The surface corresponding to the galectin carbohydrate binding site is blocked, and rotavirus VP8* instead binds siatic acid in a shallow groove between its two beta-sheets. There appears to be a small induced fit on binding. The residues that contact sialic acid are conserved in sialic acid-dependent rotavirus strains. Neutralization escape mutations are widely distributed over the VP8* surface and cluster in four epitopes. From the fit of the VP8* core into the virion spikes, we propose that VP4 arose from the insertion of a host carbohydrate binding domain into a viral membrane interaction protein.
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