Embedded within the second helical element of the LHR is an arginine (Arg413) that participates in electrostatic interactions with the coiled coil (Fig. 1C ). This residue is conserved in HTLV-1 and is critical to the inhibitory activity of the HTLV-1 LHR mimetic peptide P cr -400 [22] . Intriguingly, Arg413 projects back along the axis of the coiled coil and binds between Leu407 and Leu410, where it forms hydrogen bonds with Gln343 from the same Nhelix and Asp342 from an adjacent N-helix and also donates a hydrogen bond, through the e-nitrogen, to the main chain carbonyl of Glu408 of the LHR (Fig. 1C) . The substitution of Arg413 with alanine dramatically disrupts the fusogenic activity of envelope and reduces envelope function by more than 90% relative to wild type (Fig. 2C) . Moreover, Arg413 cannot be functionally replaced by lysine. The R413K mutant, while more fusogenic than the alanine substituted derivative, is still 85% less effective at catalysing membrane fusion than wild-type envelope (Fig. 2C) . These data indicate that the electrostatic and hydrogen bonding interactions made by Arg413 are essential to the envelope-mediated membrane fusion process.