FEATURES

FAMILY

DESCRIPTION

Also known as VP4_ROTSH, VP4. 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 (PubMed:1649333). 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 (PubMed:9144247, PubMed:15165605). It is subsequently lost, together with VP7, following virus entry into the host cell (PubMed:15165605). Following entry into the host cell, low intracellular or intravesicular Ca(2+) concentration probably causes the calcium-stabilized VP7 trimers to dissociate from the virion. This step is probably necessary for the membrane-disrupting entry step and the release of VP4, which is locked onto the virion by VP7. During the virus exit from the host cell, VP4 seems to be required to target the newly formed virions to the host cell lipid rafts (By similarity)., Forms the spike 'foot' and 'body' and acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. This reorganization may be linked to membrane penetration by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment., Forms the head of the spikes and mediates the recognition of specific host cell surface glycans. 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. In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry. Homotrimer. VP4 adopts a dimeric appearance above the capsid surface, while forming a trimeric base anchored inside the capsid layer. Only hints of the third molecule are observed above the capsid surface. It probably performs a series of molecular rearrangements during viral entry. Prior to trypsin cleavage, it is flexible. The priming trypsin cleavage triggers its rearrangement into rigid spikes with approximate two-fold symmetry of their protruding parts. After an unknown second triggering event, cleaved VP4 may undergo another rearrangement, in which two VP5* subunits fold back on themselves and join a third subunit to form a tightly associated trimer, shaped like a folded umbrella (By similarity). Interacts with VP6 (By similarity). Interacts with VP7 (By similarity).

EXTERNAL LINKS

VP4

Outer capsid protein VP4

Structural Ligandability

Domains Chains

0 chains assessed

VP4

Structural Ligandability

Domains Chains

Distribution