期刊
JOURNAL OF VIROLOGY
卷 80, 期 3, 页码 1513-1523出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.80.3.1513-1523.2006
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资金
- NCRR NIH HHS [P41 RR002250, P41 RR007707] Funding Source: Medline
- NIAID NIH HHS [P01 AI057788, R01 AI036040, R37 AI 36040, R01 AI053174, R37 AI036040, R01 AI 053174] Funding Source: Medline
The most intensively studied rotavirus strains initially attach to cells when the heads of their protruding spikes bind cell surface sialic acid. Rotavirus strains that cause disease in humans do not bind this ligand. The structure of the sialic acid binding head (the VP8* core) from the simian rotavirus strain RRV has been reported, and neutralization epitopes have been mapped onto its surface. We report here a 1.6-angstrom resolution crystal structure of the equivalent domain from the sialic acid-independent rotavirus strain DS-1, which causes gastroenteritis in humans. Although the RRV and DS-1 VP8* cores differ functionally, they share the same galectin-like fold. Differences between the RRV and DS-1 VP8* cores in the region that corresponds to the RRV sialic acid binding site make it unlikely that DS-1 VP8* binds an alternative carbohydrate ligand in this location. In the crystals, a surface cleft on each DS-1 VP8* core binds N-terminal residues from a neighboring molecule. This cleft may function as a ligand binding site during rotavirus replication. We also report an escape mutant analysis, which allows the mapping of heterotypic neutralizing epitopes recognized by human monoclonal antibodies onto the surface of the VP8* core. The distribution of escape mutations on the DS-1 VP8* core indicates that neutralizing antibodies that recognize VP8* of human rotavirus strains may bind a conformation of the spike that differs from those observed to date.
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