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Crystal Structure of the Rhesus Rotavirus VP5 Antigen Domain DimerCrystal Structure of the Rhesus Rotavirus VP5 Antigen Domain Dimer
Structural highlights
FunctionVP4_ROTRH 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. It is subsequently lost, together with VP7, following virus entry into the host cell. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. In sialic acid-dependent and/or integrin-dependent strains, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.[1] 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.[2] 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.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe spike protein VP4 is a key component of the membrane penetration apparatus of rotavirus, a nonenveloped virus that causes childhood gastroenteritis. Trypsin cleavage of VP4 produces a fragment, VP5*, with a potential membrane interaction region, and primes rotavirus for cell entry. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. Here, we report that a globular domain of VP5*, the VP5* antigen domain, is an autonomously folding unit that alternatively forms well-ordered dimers and trimers. Because the domain contains heterotypic neutralizing epitopes and is soluble when expressed directly, it is a promising potential subunit vaccine component. X-ray crystal structures show that the dimer resembles the spike body on trypsin-primed virions, and the trimer resembles the folded-back form of the spike. The same structural elements pack differently to form key intermolecular contacts in both oligomers. The intrinsic molecular property of alternatively forming dimers and trimers facilitates the VP5* reorganization, which is thought to mediate membrane penetration during cell entry. Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement.,Yoder JD, Dormitzer PR EMBO J. 2006 Apr 5;25(7):1559-68. Epub 2006 Mar 2. PMID:16511559[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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