The structure of the BLV TM ectodomain To obtain crystals for structural studies, the N-and C-terminal limits of the coiled coil region of BLV TM were identified using LearnCoil VMF [25] . The TM ectodomain, including the predicted coiled coil and LHR from Ala326 to Trp418, were fused to the C-terminal end of maltose binding protein via a threealanine spacer following the methodology of Center et al [26] . The soluble purified protein was crystallised and the structure solved to a resolution of 2.0 Å (Fig. 1 ). As anticipated, the overall fold of the BLV TM ectodomain is that of a trimer-of-hairpins, with the Nterminal a-helices twisting around each other to produce the central triple-stranded coiled coil that is characteristic of class I fusion proteins. Buried leucine and isoleucine residues within the coiled coil predominantly mediate the interactions between monomers, but strikingly there are two polar layers within the coiled coil that establish interactions with ordered water molecules and a chloride ion respectively (see below). At the base of the coiled coil the peptide backbone undergoes a 180u loop forming the chain reversal region (Fig. 1A, B) , within which is a short helical segment containing the first cysteine of the conserved CX 6 CC motif [9, 10] . The predicted disulphide between Cys384 and Cys391 is reduced in the resolved structure but this does not appear to affect the overall protein fold. In support of this view, preliminary lower resolution structures obtained for crystals formed in the absence of TCEP-HCL reveal an intact disulphide (data not shown). These data indicate that the disulphide is not essential for constraining the chain reversal region in the folded protein, even though it might play a role in the folding process. Therefore, the known defects in membrane fusion associated with substitution of these cysteines are likely due to direct perturbation of the inter-subunit disulphide isomerisation step of the envelopemediated membrane fusion process [9, 10] . After Cys391, the LHR begins with an extended non-helical leash followed by an eightresidue a-helix. This helix is followed by a three-residue linker incorporating a single proline, allowing a sharp kink in the LHR prior to the start of a second a-helix that adopts an orientation almost 90u to the first helical segment of the LHR (Fig. 1A , B, C).