Gp41
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Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex of retroviruses, including Human immunodeficiency virus (HIV). Gp41 is a transmembrane protein that contains several sites within its ectodomain that are required for infection of host cells.
Contents
Gene and post-translational modifications
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The env gene codes for gp160, a precursor, which is extensively glycosylated and proteolytically cleaved into two subunits gp120 and gp41 (this protein) by furin, a host cellular protease.
Function
In a free virion, the fusion peptides at the amino termini of gp41 are buried within the envelope complex in an inactive non-fusogengic state that is stabilized by a non-covalent bond with gp120. Gp120 binds to a CD4 and a co-receptor (CCR5 or CXCR4), found on susceptible cells such as Helper T cells and macrophages.[1] As a result, a cascade of conformational changes occurs in the gp120 and gp41 proteins. The core of gp41 folds into a six helical bundle structure exposing the previously hidden gp41 fusion peptides which then assist in the fusion with the host cell.[2] The activation process occurs readily which suggest that the inactive state of gp41 is metastable and the conformational changes allow gp41 to achieve its more stable active state.
As a drug target
The interaction of gp41 fusion peptides with the target cell causes a formation of an intermediate, pre-hairpin structure which bridges and fuses the viral and host membranes together. The pre-hairpin structure has a relatively long half-life which makes it a target for therapeutic intervention and inhibitory peptides.[3]
Enfuvirtide (also known as T-20) is a fusion inhibitor drug that binds to the pre-hairpin structure and prevents membrane fusion and HIV-1 entry to the cell. The vulnerability of this structure has initiated development towards a whole spectrum of fusion preventing drugs.[4] A variety of naturally-occurring molecules have also been shown to bind gp41 and prevent HIV-1 entry. [5]
References
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<references />, or <references group="..." />External links
- gp41 Envelope Protein, HIV at the US National Library of Medicine Medical Subject Headings (MeSH)
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