Along the length of the LHR multiple contacts are made with the coiled coil and such interactions are required for the activity of inhibitory LHR-mimetic peptides [14, 17, 21, 22] . Amino acid residues that are critical determinants of peptide potency map to the C-terminal region of the LHR [21, 22] , but key residues and the manner in which they interact with the coiled coil are not resolved in the published HTLV-1 TM structure [20] . A detailed view of the BLV LHR bound to the coiled coil and a sequence comparison of the HTLV-1 and BLV LHRs are shown in Fig. 1C and D. Towards the N-terminus of the BLV LHR, conserved residues Leu394 and Ile396 dock into a hydrophobic pocket on the coiled coil, and an array of polar side chains at one side of the pocket interact with the LHR peptide backbone (Fig. 1C) . We have previously demonstrated that interactions with the peptide backbone contribute to the activity of the BLV and HTLV-1 peptide inhibitors [17, 22] . By contrast, the side chain of Arg395 projects out into solvent suggesting that this residue is not essential for interaction of the LHR with the coiled coil or for trimer-ofhairpins formation (Fig. 1C ). In keeping with this view, the R395A substitution has no significant effect on envelope fusogenicity (Fig. 2C) and therefore serves as a useful control for our analysis of envelope structure and function. As the N-helices twist around one another the groove between them accommodates the first conserved a-helical segment of the LHR. Within this a-helix, BLV residues Ile401 and Leu404 extend down and pack into the groove (Fig. 1C) . Significantly, substitution of Leu404 with alanine results in an 80% loss of fusogenic activity relative to wild type (Fig. 2C) , indicating that this interaction contributes substantially to the stability of the LHR/coiled coil interaction.