Coiled-coil motif as a structural basis for the interaction of HTLV type 1tax with cellular cofactors

Human T lymphotropic virus type 1 (HTLV-1) Tax is a multifunctional protein centrally involved in transcriptional regulation, cell cycle control, and viral transformation. The regulatory functions of Tax are thought to be med iated through protein-protein interaction with cellular cofactors, Previous ly we have identified several novel binding partners for Tax, including hum an mitotic checkpoint protein MAD1 (TXBP181), G-protein pathway suppressor GPS2 (TXBP31), and I kappaB kinase regulatory subunit IKK-gamma, Here we de scribed two additional Tax partners, TXBP151 and TXBP121. A closer examinat ion of the sequences of eight independent cellular Tax-binding proteins ide ntified by us and others revealed that all of them share a single character istic, a highly structured coiled-coil domain, We also noted that Tax and t he Tax-binding coiled-coil proteins can homodimerize. Additionally, the sam e domain in Tax is responsible for interaction with different coiled-coil p roteins, Taken together, our findings point to a particular coiled-coil str ucture as one of the Tax-recognition motifs, The interaction of Tax with a particular subgroup of cellular coiled-coil proteins represents one mechani sm by which Tax dysregulates cell growth and proliferation.