3tay

Crystal structure of porcine rotavirus CRW-8 VP8* in complex with N-glycolylneuraminic acid

spinqualitylabelsall models 3tay, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tay is a 2 chain structure with sequence from Porcine rotavirus (serotype 3 / strain crw-8). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BEN, EPE, MN0, MPD, NA, SO4 Related: 3tb0 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [VP4_ROTP3] Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. According to the considered strain, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1 (By similarity). Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment (By similarity). VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact (By similarity). Publication Abstract from PubMed The rotavirus spike protein domain VP8* is essential for recognition of cell-surface carbohydrate receptors, notably those incorporating N-acylneuraminic acids (members of the sialic acid family). N-acetylneuraminic acids occur naturally in both animals and humans whereas N-glycolylneuraminic acids are present only through dietary uptake in normal human tissues. The preference of animal rotaviruses towards these natural N-acylneuraminic acids has not been comprehensively established, and detailed structural information regarding the interactions of different rotaviruses with N-glycolylneuraminic acids is lacking. In this study, distinct specificities of VP8* towards N-acetyl- and N-glycolylneuraminic acids were revealed using biophysical techniques. VP8* protein from porcine rotavirus CRW-8 and bovine rotavirus NCDV showed preference for N-glycolyl- over N-acetylneuraminic acids, contrasting with monkey rotavirus RRV. Crystallographic structures of VP8* from CRW-8 and RRV with bound methyl N-glycolylneuraminide revealed the atomic details of their interactions. We examined the influence of amino acid type at position 157, which is proximal to the ligand's N-acetyl- or N-glycolyl-moiety and can mutate upon cell culture adaptation. A structure-based hypothesis derived from these results could account for rotavirus discrimination between the N-acylneuraminic acid forms. Infectivity blockade experiments demonstrated that the determined carbohydrate specificities of these VP8* directly correlate with those of the corresponding infectious virus. This includes an association between CRW-8 adaption to cell culture, decreased competition by N-glycolylneuraminic acid for CRW-8 infectivity, and a Pro157 to Ser157 mutation in VP8* that reduces binding affinity for N-glycolylneuraminic acid. Structural basis of rotavirus strain preference towards N-acetyl- or N-glycolylneuraminic acid-containing receptors.,Yu X, Dang VT, Fleming FE, von Itzstein M, Coulson BS, Blanchard H J Virol. 2012 Oct 3. PMID:23035213 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat protein

Proteopedia Page Contributors and Editors (what is this?)

OCA