HIV-1 glycoprotein 41 membrane-proximal external region (gp41 MPER)

The HIV-1 glycoprotein 41 (gp41) membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich segment of the HIV-1 envelope protein located adjacent to the viral transmembrane domain (Montero et al., 2008, Microbiology and Molecular Biology Reviews). It plays a critical role in the late stages of viral entry by facilitating the fusion between the viral envelope and the host cell plasma membrane. The MPER is a primary target for broadly neutralizing antibodies (bNAbs), such as 2F5, which recognize specific linear epitopes (e.g., ELDKWA) within this region to block the conformational changes necessary for fusion (Huang et al., 2012, Nature). Because of its high conservation across diverse HIV-1 clades, the gp41 MPER is a major focus in the development of prophylactic vaccines and passive immunization therapies. However, drug development targeting this region faces challenges, including the partial burial of the MPER in the viral lipid bilayer and the potential for antibodies to cross-react with host lipids like cardiolipin (Haynes et al., 2005, Science). Understanding the structural dynamics of the MPER remains essential for designing immunogens that can elicit a robust and broad protective immune response against HIV-1.

Other names

MPERgp41 membrane-proximal external region2F5 epitopeHIV-1 gp41 MPERMembrane-proximal external region of gp41

Neutralization of HIV-1 by binding to the gp41 MPER, which inhibits the transition of the envelope glycoprotein from a pre-hairpin intermediate to a six-helix bundle, thereby blocking viral-host cell membrane fusion (Buzon et al., 2010, PLoS Pathogens).