Human immunodeficiency virus type 1 glycoprotein 41 membrane-proximal external region (HIV-1 gp41 MPER) (HIV-1 gp41 MPER)

The HIV-1 gp41 membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich sequence located at the C-terminal end of the gp41 ectodomain, immediately preceding the transmembrane domain (Montero et al., 2008, PMID: 18772287). During HIV-1 entry, the envelope glycoprotein complex (gp120/gp41) undergoes conformational changes upon binding to CD4 and coreceptors, leading to the formation of a transient pre-hairpin intermediate where the MPER is exposed (Frey et al., 2008, PMID: 18332424). This intermediate state is a critical target for broadly neutralizing antibodies (bNAbs) such as 2F5, 4E10, and 10E8, which bind to the MPER and block the transition to the post-fusion six-helix bundle, thereby preventing viral-cell membrane fusion (Huang et al., 2012, PMID: 23151583). Because the MPER is essential for the fusion process and is highly conserved across diverse HIV-1 strains, it is a primary focus for vaccine design and the development of fusion-inhibitor drugs (Kim et al., 2014, PMID: 24501411). However, therapeutic targeting is complicated by the MPER's close proximity to the viral lipid bilayer and its limited accessibility during the short-lived pre-hairpin stage (Ofek et al., 2004, PMID: 15548732).

Other names

MPERgp41 MPERMembrane-proximal external regionHIV-1 gp41 pre-hairpin intermediategp41 MPER epitope

Inhibition of viral-cell membrane fusion by binding to the transiently exposed pre-hairpin intermediate of gp41, preventing the formation of the six-helix bundle (Zhu et al., 2013, PMID: 23596311).