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

The HIV-1 envelope glycoprotein gp41 is a transmembrane protein that plays a vital role in the infection process by facilitating the fusion of the viral envelope with the host cell membrane (UniProt P04578). The Membrane Proximal External Region (MPER) is a highly conserved, tryptophan-rich sequence located at the C-terminal end of the gp41 ectodomain, immediately adjacent to the transmembrane anchor (PubMed: 11069991). This region is a major target for broadly neutralizing antibodies (bnAbs) like 2F5, which recognizes the conserved ELDKWA motif (PubMed: 11069991). Binding of these antibodies to the MPER prevents the structural rearrangements of gp41 necessary for membrane fusion, effectively neutralizing the virus (PubMed: 23151583). Despite its conservation, the MPER is difficult to target because it is partially buried in the viral membrane and only fully exposed during the transient fusion process (PubMed: 15661917). Research into MPER-targeting agents is a cornerstone of HIV vaccine development and passive immunization strategies. The 2F5 Fab fragment mentioned in the query is a specific antibody component used to study the structural basis of this neutralization (PubMed: 11069991). Therapeutic challenges include the potential for auto-reactivity due to the lipid-binding properties of many MPER-directed antibodies (PubMed: 15661917).

Other names

gp41Transmembrane glycoprotein gp41MPERMembrane proximal external regionHIV-1 Env gp41

Neutralization of viral infectivity by binding to the MPER of gp41, thereby sterically hindering the conformational transitions of the envelope glycoprotein required for fusion between the viral envelope and the host cell plasma membrane.