Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein

We have developed a genetic method to determine the active orientation of d imeric transmembrane protein helices, The bovine papillomavirus E5 protein, a 44-amino acid homodimeric protein that appears to traverse membranes as a left-handed foiled-coil, transforms fibroblasts by binding and activating the platelet-derived growth factor (PDCF) beta receptor, A heterologous di merization domain was used to force E5 monomers to adopt all seven possible symmetric coiled-coil registries relative to one another within the dimer, Focus formation assays demonstrated that dimerization of the E5 protein is required for transformation and identified a single preferred orientation of the monomers, The essential glutamine residue at position 17 resided in the dimer interface in this active orientation, The active chimera formed c omplexes with the PDGF beta receptor and induced receptor tyrosine phosphor ylation, We also identified ES-like structures that underwent non-productiv e interactions with the receptor.