HIV-1 envelope glycoprotein gp41 membrane-proximal external region (MPER) (HIV-1 gp41 MPER)

The HIV-1 envelope glycoprotein gp41 membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich segment located at the C-terminal end of the gp41 ectodomain, adjacent to the transmembrane domain (PMID: 22106361). It plays a vital role in the fusion of the viral and host cell membranes by stabilizing the pre-hairpin intermediate and facilitating the formation of the six-helix bundle (PMID: 15661915). Because of its critical function and high sequence conservation across various HIV-1 strains, the MPER is a key target for broadly neutralizing antibodies (bNAbs) such as 2F5, 4E10, and 10E8 (PMID: 23021216). These antibodies neutralize the virus by binding to the MPER during the fusion process, thereby preventing the entry of the viral genome into the host cell (PMID: 24089446). However, the MPER is relatively inaccessible to the immune system due to steric hindrance from the gp120/gp41 trimer and its proximity to the viral lipid bilayer (PMID: 21835245). Additionally, some MPER-targeting antibodies show polyreactivity with host lipids, which poses a significant challenge for vaccine design and therapeutic development due to potential safety concerns (PMID: 15845852).

Other names

MPERMembrane-proximal external regiongp41 MPER epitopeHIV-1 gp41 MPERgp41 MPER domain

Neutralization of HIV-1 by binding to the MPER of gp41, which prevents the formation of the six-helix bundle and inhibits the fusion of viral and host cell membranes (PMID: 15661915, PMID: 23021216).