Envelope glycoprotein gp160

Details

Name
Envelope glycoprotein gp160
Synonyms
  • Env polyprotein
Gene Name
env
Organism
HIV-1
Amino acid sequence
>lcl|BSEQ0012338|Envelope glycoprotein gp160
MRATEIRKNYQHLWKGGTLLLGMLMICSAAEQLWVTVYYGVPVWKEATTTLFCASDAKAY
DTEVHNVWATHACVPTDPNPQEVKLENVTENFNMWKNNMVEQMHEDIISLWDQSLKPCVK
LTPLCVTLNCTDLRNATNTTSSSWETMEKGEIKNCSFNITTSIRDKVQKEYALFYNLDVV
PIDNASYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNDKKFNGTGPCTNVST
VQCTHGIRPVVSTQLLLNGSLAEEEIVIRSENFTNNAKTIIVQLNESVVINCTRPNNNTR
KSINIGPGRALYTTGEIIGDIRQAHCNLSKTQWENTLEQIAIKLKEQFGNNKTIIFNPSS
GGDPEIVTHSFNCGGEFFYCNSTQLFTWNDTRKLNNTGRNITLPCRIKQIINMWQEVGKA
MYAPPIRGQIRCSSNITGLLLTRDGGKDTNGTEIFRPGGGDMRDNWRSELYKYKVVKIEP
LGVAPTKAKRRVVQREKRAVGLGALFLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQN
NLLRAIEAQQHLLQLTVWGIKQLQARVLAVERYLRDQQLLGIWGCSGKLICTTTVPWNTS
WSNKSLNEIWDNMTWMKWEREIDNYTHIIYSLIEQSQNQQEKNEQELLALDKWASLWNWF
DITKWLWYIKIFIMIVGGLIGLRIVFVVLSIVNRVRQGYSPLSFQTHLPAQRGPDRPDGI
EEEGGERDRDRSGPLVDGFLAIIWVDLRSLCLFSYHRLRDLLLIVTRIVELLGRRGWGVL
KYWWNLLQYWIQELKNSAVSLLNATAIAVAEGTDRVIEILQRAFRAVLHIPVRIRQGLER
ALL
Number of residues
843
Molecular Weight
95647.42
Theoretical pI
8.63
GO Classification
Functions
structural molecule activity
Processes
apoptotic process / clathrin-mediated endocytosis of virus by host cell / evasion or tolerance by virus of host immune response / fusion of virus membrane with host endosome membrane / fusion of virus membrane with host plasma membrane / innate immune response / stimulatory C-type lectin receptor signaling pathway / viral protein processing / virion attachment to host cell
Components
host cell endosome membrane / host cell plasma membrane / integral component of membrane / viral envelope / virion / virion membrane
General Function
Structural molecule activity
Specific Function
Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.Surface protein gp120: 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 CXCR4 and/or CCR5. Acts as 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. HIV 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.Transmembrane protein gp41: 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 and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. 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.
Pfam Domain Function
Transmembrane Regions
672-692
Cellular Location
Virion membrane
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP35961
UniProtKB Entry NameENV_HV1Y2
General References
  1. Li Y, Hui H, Burgess CJ, Price RW, Sharp PM, Hahn BH, Shaw GM: Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation. J Virol. 1992 Nov;66(11):6587-600. [PubMed:1404605]
  2. Rizzuto CD, Wyatt R, Hernandez-Ramos N, Sun Y, Kwong PD, Hendrickson WA, Sodroski J: A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science. 1998 Jun 19;280(5371):1949-53. [PubMed:9632396]
  3. Geijtenbeek TB, van Kooyk Y: Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a pathogen receptor with broad specificity. APMIS. 2003 Jul-Aug;111(7-8):698-714. [PubMed:12974773]
  4. Gallo SA, Finnegan CM, Viard M, Raviv Y, Dimitrov A, Rawat SS, Puri A, Durell S, Blumenthal R: The HIV Env-mediated fusion reaction. Biochim Biophys Acta. 2003 Jul 11;1614(1):36-50. [PubMed:12873764]
  5. Perfettini JL, Castedo M, Roumier T, Andreau K, Nardacci R, Piacentini M, Kroemer G: Mechanisms of apoptosis induction by the HIV-1 envelope. Cell Death Differ. 2005 Aug;12 Suppl 1:916-23. [PubMed:15719026]
  6. Hartley O, Klasse PJ, Sattentau QJ, Moore JP: V3: HIV's switch-hitter. AIDS Res Hum Retroviruses. 2005 Feb;21(2):171-89. [PubMed:15725757]
  7. Reeves JD, Piefer AJ: Emerging drug targets for antiretroviral therapy. Drugs. 2005;65(13):1747-66. [PubMed:16114975]
  8. Lusso P: HIV and the chemokine system: 10 years later. EMBO J. 2006 Feb 8;25(3):447-56. Epub 2006 Jan 26. [PubMed:16437164]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04639BiphenylalanineexperimentalunknownDetails
DB11854AstodrimerinvestigationalunknownDetails