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The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site
Author(s) -
Dormitzer Philip R.,
Sun ZhenYu J.,
Wagner Gerhard,
Harrison Stephen C.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.5.885
Subject(s) - biology , sialic acid , n acetylneuraminic acid , galectin , binding site , rotavirus , binding domain , virology , biochemistry , virus
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 β‐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 sialic acid in a shallow groove between its two β‐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.