Content deleted Content added
Citation bot (talk | contribs) m Alter: doi. | You can use this bot yourself. Report bugs here. | Activated by User:Awkwafaba | via #UCB_webform |
Citation bot (talk | contribs) Add: doi-access. | Use this bot. Report bugs. | #UCB_CommandLine |
||
(15 intermediate revisions by 8 users not shown) | |||
Line 1:
{{Pfam box
''Env'' is a viral gene that encodes the protein forming the [[viral envelope]].<ref>{{MeshName|Gene+Products,+env}}</ref> The expression of the ''env'' gene enables [[retrovirus]]es to target and attach to specific cell types, and to infiltrate the target cell membrane.<ref name="Coffin_1997">{{cite book |vauthors=Coffin JM, Hughes SH, Vamus HE | title = Retroviruses | publisher = Cold Spring Harbor Laboratory Press | location = Plainview, N.Y | year = 1997 | pages = | isbn = 978-0-87969-497-5 | oclc = | doi = | accessdate = }}</ref>▼
|Name={{abbr|TLV|T-cell leukemia virus}}/ENV coat polyprotein
|InterPro=IPR018154
|Pfam=PF00429
|Symbol=TLV_coat
}}
▲''Env'' is a viral gene that encodes the protein forming the [[viral envelope]].<ref>{{MeshName|Gene+Products,+env}}</ref> The expression of the ''env'' gene enables [[retrovirus]]es to target and attach to specific cell types, and to infiltrate the target [[cell membrane]].<ref name="Coffin_1997">{{cite book |vauthors=Coffin JM, Hughes SH, Vamus HE | title = Retroviruses | publisher = Cold Spring Harbor Laboratory Press | location = Plainview, N.Y | year = 1997
Analysis of the structure and sequence of several different ''env'' genes suggests that '''Env''' proteins are [[Fusion_mechanism#Class_I_Fusogens|type 1 fusion
While there are significant differences in sequence of the ''env'' gene between
The mature product of the ''env'' gene is the viral spike protein, which has two main parts: the surface protein (SU) and the transmembrane protein (TM). The [[Viral tropism|tropism]] of the virus is determined by the SU protein domain because it is responsible for the receptor-binding function of the virus. The SU domain therefore determines the specificity of the virus for a single receptor molecule.<ref name="Coffin_1997"/>
Line 11 ⟶ 17:
=== Oligomerization ===
The retroviral glycoproteins are oligomeric complexes that are composed of SU-TM [[heterodimer]]s, which are made in the [[endoplasmic reticulum]] after the translation of the glycosylated Env precursor.<ref name="pmid2847170">{{cite journal |vauthors=Einfeld D, Hunter E | title = Oligomeric structure of a prototype retrovirus glycoprotein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 22 | pages = 8688–92 |date=November 1988 | pmid = 2847170 | pmc = 282525 | doi =10.1073/pnas.85.22.8688 | bibcode = 1988PNAS...85.8688E | doi-access = free }}</ref> The arrangement of these heterodimers determines the 3D structure of the knobbed spike on the viral surface. The Env proteins of the Avian Sarcoma and Leukosis virus ([[Avian sarcoma leukosis virus|ASLV]]) and the Murine Leukemia Virus ([[Murine leukemia virus|MLV]]) are both trimers of SU-TM heterodimers.<ref name="pmid1887590">{{cite journal |vauthors=Kamps CA, Lin YC, Wong PK | title = Oligomerization and transport of the envelope protein of Moloney murine leukemia virus-TB and of ts1, a neurovirulent temperature-sensitive mutant of MoMuLV-TB | journal = Virology | volume = 184 | issue = 2 | pages = 687–94 |date=October 1991 | pmid = 1887590 | doi =10.1016/0042-6822(91)90438-H }}</ref> The Env protein of Human Immunodeficiency Virus ([[HIV]]) also has a trimeric structure of heterodimers.<ref name="pmid22807678">{{cite journal |vauthors=Tran EE, Borgnia MJ, Kuybeda O, Schauder DM, Bartesaghi A, Frank GA, Sapiro G, Milne JL, Subramaniam S | title = Structural mechanism of trimeric HIV-1 envelope glycoprotein activation | journal =
=== Post-translational modification ===
Line 19 ⟶ 25:
== In HIV ==
[[File:HI-virion-structure en.svg|thumb|300px|Diagram of HIV virion]]
The ''env'' gene codes for the gp160 protein which forms a homotrimer, and is cleaved into gp120 and gp41 by the host cell [[protease]], [[furin]]. To form an active fusion protein, SU gp120 and TM gp41 polypeptides remain non-covalently bound together, but this interaction is often not stable, leading to shed, soluble gp120 and membrane-bound, gp41 'stumps'. Separately, cleavage by furin is inefficient, and virions often are released with inactive, uncleaved gp160. Because of the high prevalence of these inactive forms, the immune system often produces [[antibodies]] which target inactive
''Env'' expression is regulated by the gene product of ''[[Rev (HIV)|rev]]''. Experimental deletion of ''rev'' resulted in the inability to detect the Env protein and levels of ''env'' mRNA in the cell cytoplasm were significantly diminished. However, when total cellular RNA was analyzed, ''env'' RNA totals were not significantly
{{Infobox nonhuman protein
Line 46 ⟶ 52:
===gp120===
{{main|gp120}}
Exposed on the surface of the viral envelope, the [[glycoprotein]] gp120 binds to the [[CD4]] [[receptor (biochemistry)|receptor]] on any target cell that has such a receptor, particularly the [[helper T-cell
Since CD4 receptor binding is the most obvious step in HIV infection, gp120 was among the first targets of [[HIV vaccine]] research. These efforts have been hampered by the fusion mechanism used by HIV, which makes neutralization by antibodies extremely difficult. Prior to binding the host cell, gp120 remains effectively hidden from antibodies because it is buried in the protein and shielded by sugars. Gp120 is only exposed when in close proximity to a host cell and the space between the viral and host cell membranes is small enough to sterically hinder the binding of antibodies.<ref name="pmid12970440">{{cite journal |vauthors=Labrijn AF, Poignard P, Raja A, Zwick MB, Delgado K, Franti M, Binley J, Vivona V, Grundner C, Huang CC, Venturi M, Petropoulos CJ, Wrin T, Dimitrov DS, Robinson J, Kwong PD, Wyatt RT, Sodroski J, Burton DR | title = Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus type 1 | journal = J. Virol. | volume = 77 | issue = 19 | pages = 10557–65 |date=October 2003 | pmid = 12970440 | pmc = 228502 | doi =10.1128/JVI.77.19.10557-10565.2003 }}</ref>
Line 54 ⟶ 60:
The glycoprotein gp41 is non-[[covalent bond|covalently]] bound to gp120, and provides the second step by which [[viral entry|HIV enters]] the cell. It is originally buried within the viral envelope, but when gp120 binds to a CD4 receptor, gp120 changes its [[chemical conformation|conformation]] causing gp41 to become exposed, where it can assist in fusion with the host cell.
[[Fusion inhibitor]] drugs such as [[enfuvirtide]] block the fusion process by binding to gp41.<ref name="pmid12637625">{{cite journal |author9-link=Daniel Kuritzkes|vauthors=Lalezari JP, Henry K, O'Hearn M, Montaner JS, Piliero PJ, Trottier B, Walmsley S, Cohen C, Kuritzkes DR, Eron JJ, Chung J, DeMasi R, Donatacci L, Drobnes C, Delehanty J, Salgo M | title = Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America | journal = N. Engl. J. Med. | volume = 348 | issue = 22 | pages = 2175–85 |date=May 2003 | pmid = 12637625 | doi = 10.1056/NEJMoa035026 | doi-access = free }}</ref>
== Env in MMTV ==
Line 70 ⟶ 76:
== Env in MLV ==
The ''env'' gene of [[Murine leukemia virus|Murine Leukemia Virus]] (MLV) codes for the 71,000-dalton glycoprotein, gp71. This membrane receptor was isolated from Rauscher murine leukemia virus (R-MuLV).<ref name="pmid8213">{{cite journal |vauthors=DeLarco J, Todaro GJ | title = Membrane receptors for murine leukemia viruses: characterization using the purified viral envelope glycoprotein, gp71 | journal = Cell | volume = 8 | issue = 3 | pages = 365–71 |date=July 1976 | pmid = 8213 | doi =10.1016/0092-8674(76)90148-3 | s2cid = 45192638 }}</ref>
== Env in mammalian evolution ==
The retroviral protein env has been captured multiple times during [[mammalian evolution]] and is expressed in placental tissue, where it facilitates fusion of fetal and maternal cells. The protein is called [[syncytin]] in mammals.<ref>Nova. 2016. Endogenous retroviruses. Retrieved from https://www.pbs.org/wgbh/nova/next/evolution/endogenous-retroviruses</ref><ref name="pmid23938756">{{cite journal | vauthors = Lavialle C, Cornelis G, Dupressoir A, Esnault C, Heidmann O, Vernochet C, Heidmann T | title = Paleovirology of 'syncytins', retroviral env genes exapted for a role in placentation | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 368 | issue = 1626 | pages = 20120507 | date = September 2013 | pmid = 23938756 | pmc = 3758191 | doi = 10.1098/rstb.2012.0507 }}</ref>
== See also ==
* [[Viral structural protein]]
== References ==
Line 85 ⟶ 95:
{{Viral proteins}}
[[Category:Viral structural proteins]]
|