1KQR: Crystal Structure Of The Rhesus Rotavirus Vp4 Sialic Acid Binding Domain In Complex With 2-o-methyl-alpha-d-n-acetyl Neuraminic Acid

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 sialic 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.
PDB ID: 1KQRDownload
MMDB ID: 71265
PDB Deposition Date: 2002/1/7
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 1KQR: monomeric; determined by author
Molecular Components in 1KQR
Label Count Molecule
Protein (1 molecule)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB