HIV-1 envelope glycoprotein 41 membrane-proximal external region (MPER)

The HIV-1 envelope glycoprotein 41 membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich segment of the gp41 transmembrane subunit located immediately adjacent to the viral lipid bilayer (UniProt: P04578). It plays a critical role in the viral entry process by facilitating the fusion of the HIV-1 envelope with the host cell plasma membrane during the final stages of infection. Because its sequence is remarkably stable across diverse HIV-1 clades, MPER is a primary target for the development of broadly neutralizing antibodies (bNAbs) and universal HIV vaccines (PubMed: 15661915). Antibodies such as 2F5, 4E10, and 10E8 bind to this region, effectively neutralizing the virus by arresting the conformational changes required for membrane fusion. However, the MPER is often physically shielded or partially buried within the viral membrane, making it difficult for the immune system to access. Additionally, some MPER-targeting antibodies exhibit polyreactivity with host lipids, which presents a significant challenge in designing safe and effective immunogens that do not trigger autoimmune responses (PubMed: 24089451).

Other names

Membrane-proximal external regiongp41 MPERHIV-1 gp41 MPERgp41 membrane-proximal region

Binding to the highly conserved MPER domain of the gp41 subunit to inhibit the transition of the fusion machinery from the pre-hairpin intermediate to the six-helix bundle, thereby preventing the fusion of the viral envelope with the host cell membrane (PubMed: 22114446, 23153335).