2dwr
From Proteopedia
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Crystal structure of the human Wa rotavirus VP8* carbohydrate-recognising domain
Overview
Rotavirus infection leads to the death of half a million children, annually. The exact specifics of interaction between rotavirus particles, and host cells enabling invasion and infection have remained elusive. Host, cell oligosaccharides are critical components, and their involvement aids, the virus in cell-recognition and attachment, as well as dictation of the, remarkable host-specificity that rotaviruses demonstrate. Interaction, between the rotavirus spike-protein carbohydrate-binding domain (VP8*) and, cell surface oligosaccharides facilitate virus recognition of host cells, and attachment. Rotaviruses are considered, controversially, to recognise, vastly different carbohydrate structures and either with incorporation of, terminal sialic acid or without, as assessed by their ability to infect, cells that have been pre-treated with sialidases. Herein, the X-ray, crystallographic structures of VP8* from the sialidase insensitive Wa and, the sialidase sensitive CRW-8 rotavirus strains that cause debilitating, gastroenteritis in human and pig are reported. Striking differences are, apparent regarding recognition of the sialic acid derivative methyl, alpha-d-N-acetylneuraminide, presenting the first experimental evidence of, the inability of the human rotavirus strain to bind this monosaccharide, that correlates with Wa and CRW-8 recognising sialidase-resistant and, sialidase-sensitive receptors, respectively. Identified are structural, features that provide insight in attainment of substrate specificity, exhibited by porcine strains as compared to rhesus rotavirus. Revealed in, the CRW-8 VP8* structure is an additional bound ligand that intriguingly, is within a cleft located equivalent to the carbohydrate-binding region of, galectins, and is suggestive of a new region for interaction with, cell-surface carbohydrates. This novel result and detailed comparison of, our representative sialidase-sensitive CRW-8 and insensitive Wa VP8*, structures with those reported leads to our hypothesis that this groove is, used for binding carbohydrates, and that for the human strains, as for, other sialidase-insensitive strains could represent a major, oligosaccharide-binding region.
About this Structure
2DWR is a Single protein structure of sequence from Human rotavirus a with and as ligands. Full crystallographic information is available from OCA.
Reference
Insight into Host Cell Carbohydrate-recognition by Human and Porcine Rotavirus from Crystal Structures of the Virion Spike Associated Carbohydrate-binding Domain (VP8*)., Blanchard H, Yu X, Coulson BS, von Itzstein M, J Mol Biol. 2007 Apr 6;367(4):1215-26. Epub 2007 Jan 13. PMID:17306299
Page seeded by OCA on Tue Jan 29 19:13:48 2008
