The most notable difference between the HTLV-1 and BLV TM structures is the resolution of a second helical motif within the LHR of the trimer-of-hairpins. Residues that form the start of the second a-helix are conserved in HTLV-1 and are critical to envelope-catalysed membrane fusion and to the inhibitory activity of LHR-mimetic peptides [21, 22] . Just three residues from the end of our structure is the first tryptophan of a conserved tryptophanrich membrane-proximal region (MPR). The MPR is believed to interact with the opposing membranes during the fusion process and substitution of the aromatic residues severely compromises, but does not abolish, membrane fusion [39] . The conformation of the MPR has received considerable attention because broadly neutralising anti-HIV-1 antibodies bind epitopes contained within the MPR [40, 41] . It is likely that the HIV MPR adopts a helical structure when interacting with membranes and the coiled coil during fusion [40, 42] . Examination of the BLV envelope sequence and TM structure suggests that the second helical segment of the LHR is likely to continue and that in the fusion-activated state the tryptophan-rich MPR is also helical and inserted into the membrane at an oblique angle. For the leukaemia viruses, the conserved arginine (Arg413 in BLV), assists in defining the orientation of the MPR, as the interactions of Arg413 with the coiled coil and the LHR backbone propagate a sharp kink in the LHR towards the membrane-proximal end of the coiled coil. A lysine substitution of Arg413 retains only ,10% of the fusogenic activity of wild-type envelope lending further support to this view.