Article
- The EMBO Journal (2002) 21, 885 - 897
- doi:10.1093/emboj/21.5.885
Subject Categories:
The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site
Philip R. Dormitzer1, Zhen-Yu J. Sun2, Gerhard Wagner2 and Stephen C. Harrison1,3
- Laboratory of Molecular Medicine, Enders 673, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 USA
- Howard Hughes Medical Institute and the Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
Correspondence to:
Philip R. Dormitzer, E-mail: dormitze@crystal.harvard.edu
Received 14 December 2001; Accepted 14 January 2002; Revised 14 January 2002
Abstract
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 
-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 -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.
Keywords:
- galectin,
- hemagglutinin,
- rotavirus,
- sialic acid,
- structure
