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

The Membrane Proximal External Region (MPER) of the HIV-1 envelope glycoprotein gp41 is a highly conserved, tryptophan-rich segment located adjacent to the viral transmembrane domain (PMID: 18617515). It is essential for the viral-cell membrane fusion process, acting as a hinge or anchor that facilitates the transition of gp41 into its post-fusion conformation (PMID: 22633865). The MPER is a major target for broadly neutralizing antibodies (bNAbs), most notably 2F5, which recognizes the conserved ELDKWA motif (PMID: 11069997). Because this region is critical for entry and highly conserved across diverse HIV-1 clades, it is a high-priority target for both passive immunotherapy and vaccine development (PMID: 24403135). However, the MPER is often shielded by the viral membrane or other parts of the envelope spike, making it difficult for antibodies to access (PMID: 23152514). Therapeutic challenges include the potential for MPER-targeting antibodies to exhibit polyreactivity or autoreactivity with host lipids, such as cardiolipin (PMID: 15860610).

Other names

MPERMembrane proximal external regiongp41 MPER2F5 epitopeHIV-1 gp41 MPER 2F5 epitope

Neutralization of HIV-1 by binding to the MPER region, which sterically hinders the conformational transition of gp41 into the six-helix bundle required for fusion between the viral envelope and the host cell membrane (PMID: 18617515).