Virion with gp41 forming hairpin structure Virion with gp41 fusion peptide in insertion complex N and C terminal heptad repeat helices of gp41 form six-helix bundle Authored: Morrow, MP, Bukrinsky, M, 2006-03-07 21:26:47 Edited: Gopinathrao, G, 2006-02-17 18:35:46 Pubmed11591141 Pubmed11926830 Pubmed15504864 Pubmed1629954 Pubmed2364015 Pubmed2788443 Pubmed7538176 Pubmed8612573 Pubmed9108481 Pubmed9546217 Reactome Database ID Release 43164508 Reactome, http://www.reactome.org ReactomeREACT_8010 Reviewed: Reeves, J, 2006-06-12 15:22:40 The gp41 glycoprotein contains N- and C-terminal heptad repeats, which form a stable six-helical bundle. This six-helix bundle represents a fusion-active gp41 core, and its conformation is critical for membrane fusion. Among the interactions necessary for the six helix bundle conformation is the formation of a salt bridge between the Asp632 residue in the C-terminal heptad repeat and the Lys574 terminal in the N-terminal coiled-coil. Disruption of this interaction has been found to lead to destabilization of the six helix bundle formation, with a subsequent severe reduction in viral fusion activity. Also, the N-terminal heptad repeat alone was found to be important in viral fusion, as removal or truncation of this repeat reduced the fusion activity of the peptide even when the adjacent, full length N-terminal fusion peptide was in place. The bundle itself is formed during the fusion process, prior to pore formation but after insertion of the gp41 fusion peptide into the target cell membrane. Upon insertion of the fusion peptide, the three N-terminal helices of gp41 adjacent to the target cell membrane and three C-terminal helices adjacent to the viral membrane undergo a conformational change which brings them into close proximity with one another, creating a six-helix bundle and leading to eventual fusion.<br>