HIV-1 envelope glycoprotein 41 (gp41)

HIV-1 envelope glycoprotein 41 (gp41) is the transmembrane subunit of the envelope glycoprotein complex found on the surface of HIV-1 virions, where it forms a trimeric structure in conjunction with gp120. Gp41 is produced by proteolytic cleavage of an Env precursor (gp160), and serves as the key mediator of viral and host cell membrane fusion—a critical step for HIV entry into target cells. The protein contains several distinct regions: a fusion peptide, two heptad repeat (NHR and CHR) regions, a membrane-proximal external region (MPER), a transmembrane segment, and a cytoplasmic domain[1][5][6]. Upon receptor (CD4 and co-receptor) engagement by gp120, gp41 undergoes a dramatic conformational change leading to the insertion of the fusion peptide into the host membrane and the formation of a six-helix bundle that brings viral and host membranes into proximity for fusion[2][3][7]. Gp41 is less glycosylated and more conserved than gp120, making it an attractive therapeutic and vaccine target, especially for broadly neutralizing antibodies directed to the MPER region. However, the target’s structural flexibility and antigenic masking by the viral envelope pose challenges for therapeutic intervention and vaccine design[5][6][8]. The fusion inhibitor enfuvirtide (T-20) mimics part of the heptad repeat region of gp41, disrupting bundle formation and blocking membrane fusion[6]. Resistance mutations and difficulty in eliciting high-affinity antibodies against critical gp41 epitopes remain hurdles in clinical development.

Other names

glycoprotein 41HIV gp41envelope glycoprotein 41HIV-1 gp41Human immunodeficiency virus type 1 envelope glycoprotein 41

Inhibition of viral-host membrane fusion, Blockade of heptad repeat interactions, Disruption of six-helix bundle formation