J9XVC2 · J9XVC2_SIV
- ProteinEnvelope glycoprotein gp160
- StatusUniProtKB unreviewed (TrEMBL)
- Amino acids887 (go to sequence)
- Protein existencePredicted
- Annotation score4/5
Function
function
Surface protein gp120 (SU) may target the virus to gut-associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-4/beta-7 integrins), a complex that mediates T-cell migration to the GALT. Interaction between gp120 and ITGA4/ITGB7 would allow the virus to enter GALT early in the infection, infecting and killing most of GALT's resting CD4+ T-cells. This T-cell depletion is believed to be the major insult to the host immune system leading to AIDS.
The envelope glycoprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.
The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves.
The surface protein gp120 (SU) attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CCR5. This peculiar 2 stage receptor-interaction strategy allows gp120 to maintain the highly conserved coreceptor-binding site in a cryptic conformation, protected from neutralizing antibodies. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide.
The transmembrane protein gp41 (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell endosome membrane | |
Cellular Component | host cell plasma membrane | |
Cellular Component | plasma membrane | |
Cellular Component | viral envelope | |
Cellular Component | virion membrane | |
Molecular Function | structural molecule activity | |
Biological Process | apoptotic process | |
Biological Process | membrane fusion involved in viral entry into host cell | |
Biological Process | symbiont entry into host cell | |
Biological Process | virion attachment to host cell |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameEnvelope glycoprotein gp160
- Cleaved into 2 chains
Organism names
- Strain
- Taxonomic lineageViruses > Riboviria > Pararnavirae > Artverviricota > Revtraviricetes > Ortervirales > Retroviridae > Orthoretrovirinae > Lentivirus > Simian immunodeficiency virus
Accessions
- Primary accessionJ9XVC2
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Cell membrane ; Single-pass type I membrane protein
Endosome membrane ; Peripheral membrane protein
Endosome membrane ; Single-pass type I membrane protein
Host cell membrane ; Peripheral membrane protein
Host cell membrane ; Single-pass type I membrane protein
Host endosome membrane ; Peripheral membrane protein
Host endosome membrane ; Single-pass type I membrane protein
Membrane ; Peripheral membrane protein
Membrane ; Single-pass type I membrane protein
Virion membrane ; Peripheral membrane protein
Virion membrane ; Single-pass type I membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 698-719 | Helical | ||||
Sequence: YIQYGVLIVLGVVGLRIVIYVV |
Keywords
- Cellular component
PTM/Processing
Keywords
- PTM
Interaction
Subunit
The mature envelope protein (Env) consists of a homotrimer of non-covalently associated gp120-gp41 heterodimers. The resulting complex protrudes from the virus surface as a spike. Interacts with host CD4 and CCR5 (By similarity).
Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R))
Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R))
Structure
Family & Domains
Features
Showing features for domain, coiled coil, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 24-532 | Human immunodeficiency virus 1 envelope glycoprotein Gp120 | ||||
Sequence: QYVTVFYGVPAWKNATIPLFCATRNRDTWGTTQCLPDNDDYSELAVNITEAFDAWDNTVTEQAIEDVWNLFETSIKPCVKLTPLCIAMRCNKTETDRWGLTGEAGTATTTKSTTSPTTTTVTPKVINEGDSCIKNDSCAGLEQEPMIGCKFNMTGLKRDKKTEYNETWYARDLICEQSANESESKCYMQHCNTSVIQESCDKHYWDAIRFRYCAPPGYALLRCNDSNYSGFAPNCSKVVVSSCTRMMETQTSTWFGFNGTRAENRTYIYWHGNSNRTIISLNKFYNLTMKCRRPGNKTVLPVTIMSGLVFHSQPINERPKQAWCRFGGNWSEAIQEVKETLVKHPRYTGTNETRKINLTAPAGGDPEVTFMWTNCRGEFLYCKMNWFLNWVEDRDQNGSRWKQQKNSEQQKRNYVPCHIRQIINTWHKVGKNVYLPPREGDLTCNSTVTSLIAEIDWINNNETNITMSAEVAQLYRLELGDYKLVEITPIGLAPTNVRRYTTTGASRNK | ||||||
Domain | 551-746 | Retroviral envelope protein GP41-like | ||||
Sequence: MGAASLTLSAQSRTLLAGIVQQQQQLLDVVKRQQELLRLTVWGTKNLQTRVTAIEKYLKDQAQLNSWGCAFRQVCHTTVQWPNNSLVPNWNNMTWQEWERQVDFLEANITQLLEEAQIQQEKNMYELQKLNSWDIFGNWFDLTSWLRYIQYGVLIVLGVVGLRIVIYVVQMLARLRQGYRPVFSPPPVYVQQIPIH | ||||||
Coiled coil | 645-672 | |||||
Sequence: WQEWERQVDFLEANITQLLEEAQIQQEK | ||||||
Region | 744-767 | Disordered | ||||
Sequence: PIHKDQEPPTKEGEEGEGGDRGGS | ||||||
Compositional bias | 748-764 | Basic and acidic residues | ||||
Sequence: DQEPPTKEGEEGEGGDR |
Domain
The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length887
- Mass (Da)102,186
- Last updated2012-11-28 v1
- Checksum1B26ACDC118B61CF
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 748-764 | Basic and acidic residues | ||||
Sequence: DQEPPTKEGEEGEGGDR |