HIV-1 glycoprotein 41 (gp41) (gp41)

HIV-1 glycoprotein 41 (gp41) is the transmembrane fusion protein component of the HIV-1 envelope glycoprotein complex, responsible for catalyzing the fusion of viral and cellular membranes during viral entry.[1][2] gp41 is noncovalently associated with gp120, the receptor-binding subunit, forming a trimeric spike complex on the viral surface.[2][5] Upon CD4 and coreceptor binding to gp120, gp41 undergoes a cascade of conformational changes, refolding from a metastable prefusion state into a thermodynamically stable six-helix bundle core structure that drives close apposition and fusion of viral and cellular membranes.[1][3][4] The protein contains several critical functional domains including the N-terminal fusion peptide (FP), fusion peptide proximal region (FPPR), two heptad repeat regions (HR1 and HR2), the membrane proximal external region (MPER), and transmembrane region (TMR).[7] The six-helix bundle core—composed of three N-terminal and three C-terminal helices—represents the post-fusion conformation and is the target of fusion inhibitor drugs like enfuvirtide.[3][4] gp41 is a major target for HIV therapeutics and vaccine development, with multiple broadly neutralizing antibodies targeting conserved epitopes on the MPER and other regions.[1][6][7] The structural plasticity and conformational flexibility of gp41, particularly in the membrane anchor regions, present both challenges for vaccine design and opportunities for therapeutic intervention.

Other names

Transmembrane glycoprotein (TM)Envelope transmembrane proteinHIV envelope fusion proteinHIV-1 envelope glycoprotein gp41

Fusion inhibition: Enfuvirtide binds to the pre-hairpin intermediate state of gp41 and blocks its refolding into the six-helix bundle structure, preventing membrane fusion.[1][4] - Antibody neutralization: Broadly neutralizing antibodies target conserved epitopes on the membrane proximal external region (MPER) and other gp41 regions to prevent conformational changes required for fusion.[6][7] - Entry inhibition: By blocking gp41 conformational transitions, drugs prevent the apposition of viral and cellular membranes.[1]