A9Q1L0 · VP4_ROTB2

Function

function

Outer capsid protein 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. 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. It is subsequently lost, together with VP7, following virus entry into the host cell. Following entry into the host cell, low intracellular or intravesicular Ca2+ 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.

Outer capsid protein VP5*

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.

Outer capsid protein VP8*

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.

Features

Showing features for site.

TypeIDPosition(s)Description
Site249-250Probable cleavage
Site262-263Probable cleavage

GO annotations

AspectTerm
Cellular Componenthost cell endoplasmic reticulum-Golgi intermediate compartment
Cellular Componenthost cell plasma membrane
Cellular Componenthost cell rough endoplasmic reticulum
Cellular Componentmembrane
Cellular Componentviral outer capsid
Biological Processpermeabilization of host organelle membrane involved in viral entry into host cell
Biological Processvirion attachment to host cell

Keywords

Names & Taxonomy

Protein names

Organism names

Accessions

  • Primary accession
    A9Q1L0

Proteomes

Subcellular Location

Outer capsid protein VP4

Virion
Host cell membrane
Note: The outer layer contains 180 copies of VP4, grouped as 60 dimers. Immature double-layered particles assembled in the cytoplasm bud across the membrane of the endoplasmic reticulum, acquiring during this process a transient lipid membrane that is modified with the ER resident viral glycoproteins NSP4 and VP7; these enveloped particles also contain VP4. As the particles move towards the interior of the ER cisternae, the transient lipid membrane and the non-structural protein NSP4 are lost, while the virus surface proteins VP4 and VP7 rearrange to form the outermost virus protein layer, yielding mature infectious triple-layered particles.

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00003698431-249Outer capsid protein VP8*
ChainPRO_00003698421-826Outer capsid protein VP4
ChainPRO_0000369844263-826Outer capsid protein VP5*

Post-translational modification

Outer capsid protein VP4

Proteolytic cleavage by trypsin results in activation of VP4 functions and greatly increases infectivity. The penetration into the host cell is dependent on trypsin treatment of VP4. It produces two peptides, VP5* and VP8* that remain associated with the virion. Cleavage of VP4 by trypsin probably occurs in vivo in the lumen of the intestine prior to infection of enterocytes. Trypsin seems to be incorporated into the three-layered viral particles but remains inactive as long as the viral outer capsid is intact and would only be activated upon the solubilization of the latter.

Interaction

Subunit

Outer capsid protein VP4

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. Interacts with VP6. Interacts with VP7.

Outer capsid protein VP5*

Homotrimer. The trimer is coiled-coil stabilized by its C-terminus, however, its N-terminus, known as antigen domain or 'body', seems to be flexible allowing it to self-associate either as a dimer or a trimer.

Protein-protein interaction databases

Family & Domains

Domain

Outer capsid protein VP4

The VP4 spike is divided into a foot, a stalk and body, and a head.

Sequence similarities

Belongs to the rotavirus VP4 family.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    826
  • Mass (Da)
    93,311
  • Last updated
    2008-02-05 v1
  • Checksum
    B8CC3EDD7D540505
MSLRSLLITTEAVGETTQTSDHQTSFSTRTYNEINDRPSLRVEKDGEKAYCFKNLDPVRYDTRMGEYPFDYGGQSTENNQLQFDLFTKDLMADTDIGLSDDVRDDLKRQIKEYYQQGYRAIFLIRPQNQEQQYIASYSSTNLNFTSQLSVGVNLSVLNKIQENKLHIYSTQPHIPSVGCEMITKIFRTDVDNENSLINYSVPVTVTISVTKATFEDTFVWNQNNDYPNMNYKDLIPAVTKNSIYHDVKRITKIHEYINSKKKKNGVGKIGGIQIAESKDGFWKILTKNYQIKLKFGIEGYGVMGGTFGNWLIDSGFKTVETNYEYQRNGKTINATTVASVKPSRKCGTRSPVFGQLQFSGEMMVLSHNDILTVFYTEREWALSNAIYAKNFATDFKRQFEVTAQSDELLVRTNVVPHTIKNTPGKALMEYSHGGFGQIDTSDYTGMALTFRFRCVSEDLPEGYYDKDKALTFANVGLTSFQDRQETNGTYWVYNTSTVGFGSCYPKKEFEYDINVTYTTLLPSDPEFTTGGTNYAQSVTAVLEESFINLQNQVNEMLTRMNISDLTSGVMSVFSVATSFPQILDGISDLLKAASSAFKKVKGKVGNVAKRLRGKRYVRLFDEDISIEETPRFLDSIRSSRRPSILSNMFNDDETFTALHTLASRTNSVASDVTYIQPIITTRIANSTPPVIAPASSVTYAKLKDISKIINAEIDPKSIMEFNQVSNTISILDSTKKLAQYAVDPDVIDGILNKMVGGHARSLFSLKVRKHLLDAVEKDAFVKYNYHDLMGKLLNDRELLDITNNLSSQKQFELAKEFRDLLINALA

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
EF453358
EMBL· GenBank· DDBJ
ABR32125.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

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