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Distinct insertion and inhibition mechanisms of viral TAP inhibitors. As type I membrane proteins, US6 and UL49.5 are cotranslationally inserted into the ER membrane where they subsequently inhibit TAP function. BNLF2a exploits the host Asna-1/WBR (Get3/Get1) insertion machinery for TA-anchored insertion to subsequently arrest TAP in a translocation-incompetent conformation.
