Q02837 · ENV_SIVG1

Function

function

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 (By similarity).
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 (By similarity).
The surface protein gp120 is a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they take up antigen, process it, and present it to T-cells following migration to lymphoid organs. SIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. Virion capture also seems to lead to MHC-II-restricted viral antigen presentation, and probably to the activation of SIV-specific CD4+ cells (By similarity).
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 (By similarity).
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 (By similarity).

Miscellaneous

This is an African green monkey isolate.

Features

Showing features for site.

TypeIDPosition(s)Description
Site522-523Cleavage; by host furin

GO annotations

AspectTerm
Cellular Componenthost cell endosome membrane
Cellular Componenthost cell plasma membrane
Cellular Componentmembrane
Cellular Componentviral envelope
Cellular Componentvirion membrane
Molecular Functionstructural molecule activity
Biological Processapoptotic process
Biological Processmembrane fusion involved in viral entry into host cell
Biological Processsymbiont entry into host cell
Biological Processvirion attachment to host cell

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Envelope glycoprotein gp160
  • Alternative names
    • Env polyprotein
  • Cleaved into 2 chains

Gene names

    • Name
      env

Organism names

Accessions

  • Primary accession
    Q02837

Subcellular Location

Transmembrane protein gp41

Virion membrane
; Single-pass type I membrane protein
Host cell membrane
; Single-pass type I membrane protein
Host endosome membrane
; Single-pass type I membrane protein
Note: It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag.

Surface protein gp120

Virion membrane
; Peripheral membrane protein
Host cell membrane
; Peripheral membrane protein
Host endosome membrane
; Peripheral membrane protein
Note: The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain21-705Extracellular
Transmembrane706-726Helical
Topological domain727-854Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for signal, chain, glycosylation, disulfide bond.

TypeIDPosition(s)Description
Signal1-20
ChainPRO_000003846021-522Surface protein gp120
ChainPRO_000023950721-854Envelope glycoprotein gp160
Glycosylation35N-linked (GlcNAc...) asparagine; by host
Disulfide bond42↔55
Glycosylation68N-linked (GlcNAc...) asparagine; by host
Disulfide bond99↔207
Disulfide bond106↔198
Disulfide bond111↔154
Glycosylation115N-linked (GlcNAc...) asparagine; by host
Glycosylation136N-linked (GlcNAc...) asparagine; by host
Glycosylation153N-linked (GlcNAc...) asparagine; by host
Glycosylation168N-linked (GlcNAc...) asparagine; by host
Glycosylation182N-linked (GlcNAc...) asparagine; by host
Glycosylation199N-linked (GlcNAc...) asparagine; by host
Disulfide bond220↔250
Disulfide bond230↔242
Glycosylation244N-linked (GlcNAc...) asparagine; by host
Glycosylation255N-linked (GlcNAc...) asparagine; by host
Glycosylation265N-linked (GlcNAc...) asparagine; by host
Glycosylation271N-linked (GlcNAc...) asparagine; by host
Glycosylation283N-linked (GlcNAc...) asparagine; by host
Glycosylation295N-linked (GlcNAc...) asparagine; by host
Disulfide bond300↔333
Glycosylation305N-linked (GlcNAc...) asparagine; by host
Glycosylation355N-linked (GlcNAc...) asparagine; by host
Disulfide bond382↔457
Disulfide bond389↔430
Glycosylation400N-linked (GlcNAc...) asparagine; by host
Glycosylation409N-linked (GlcNAc...) asparagine; by host
Glycosylation458N-linked (GlcNAc...) asparagine; by host
Glycosylation472N-linked (GlcNAc...) asparagine; by host
Glycosylation478N-linked (GlcNAc...) asparagine; by host
ChainPRO_0000038461523-854Transmembrane protein gp41
Glycosylation630N-linked (GlcNAc...) asparagine; by host
Glycosylation646N-linked (GlcNAc...) asparagine; by host

Post-translational modification

Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R (By similarity).

Keywords

PTM databases

Interaction

Subunit

Surface protein gp120

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))

Transmembrane protein gp41

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.

Structure

3D structure databases

Family & Domains

Features

Showing features for region, coiled coil, motif.

TypeIDPosition(s)Description
Region111-153V1
Region154-198V2
Region300-332V3
Region389-430V4
Region473-481V5
Region523-543Fusion peptide
Region586-602Immunosuppression
Coiled coil633-672
Region667-688MPER; binding to GalCer
Motif717-720YXXL motif; contains endocytosis signal

Domain

Some of the most genetically diverse regions of the viral genome are present in Env. They are called variable regions 1 through 5 (V1 through V5) (By similarity).
The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis.
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 (By similarity).

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    854
  • Mass (Da)
    96,856
  • Last updated
    1993-07-01 v1
  • Checksum
    5919CA6C9622912F
MGRLLIKILIIAIGISIGIGNLYVTVFYGIPVWKNSTVQAFCMTPNTNMWATTNCIPDDHDNTEVPLNITEAFEAWDNPLVKQAESNIHLLFEQTMRPCVKLSPICIKMSCVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNCTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHCNDSVIKEACDKTYWDTLRVRYCAPAGYALLKCNDKDYRGFAPKCKNVSVVHCTRLINTTITTGIGLNGSRSENRTEIWQKGGNDNDTVIIKLNKFYNLTVRCRRPGNKTVLPVTIMAGLVFHSQKYNTRLKQAWCHFQGDWKGAWKEVREEVKKVKNLTEVSIENIHLRRIWGDPESANFWFNCQGEFFYCKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVACHIRQVVNDWYTVSKKVYAPPREGHLECNSSVTALYVAIDYNNKSGPINVTLSPQVRSIWAYELGDYKLVEITPIGFAPTDVRRYTGPTREKRVPFVLGFLGFLGAAGTAMGAAATTLTVQSRHLLAGILQQQKNLLAAVEQQQQLLKLTIWGVKNLNARVTALEKYLEDQARLNSWGCAWKQVCHTTVPWKYNNTPKWDNMTWLEWERQINALEGNITQLLEEAQNQESKNLDLYQKLDDWSGFWSWFSLSTWLGYVKIGFLVIVIILGLRFAWVLWGCIRNIRQGYNPLPQIHIHSSAERPDNGGGQDRGGESSSSKLIRLQEESSTPSRINNWWLNFKSCSLRIRTWCYNICLTLLIFIRTAVGYLQYGLQQLQEAATGLAQALARAAREAWGRLGAIVRSAYRAVINSPRRVRQGLEKVLG

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M66437
EMBL· GenBank· DDBJ
AAA91928.1
EMBL· GenBank· DDBJ
Genomic DNA
M58410
EMBL· GenBank· DDBJ
AAA47591.1
EMBL· GenBank· DDBJ
Genomic RNA

Genome annotation databases

Similar Proteins

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