Figure 5

Configuration models of human tetherin. (A) Schematic illustrations of tetherin and Vpu. Numbers indicate amino acid positions. Critical residues of each protein are indicated. (B) Structure of tetherin. Tetherin comprises a short amino-terminal cytoplasmic tail (CT), followed by an α-helical transmembrane (TM) domain and a coiled-coil extracellular (EC) domain that is linked back to the plasma membrane by a carboxy-terminal glycophosphatidylinositol (GPI) anchor. The EC domain contains N-glycosylation sites and cysteine residues involved in disulfide-bond formation. (C-F) Configuration models of tetherin. (C) The EC self-interaction model. Individual tetherin monomers are anchored at both ends to the same membrane, with interaction between the ECs of cell-bound and virion-bound monomers. (D) Anti-parallel membrane-spanning model. Monomers are anchored in both membranes with opposing orientations. (E) Parallel membrane-spanning model. Monomers are anchored in both membranes with the same orientation. (F) HIV-1 Vpu and tetherin interact through their TM domains. Key amino acids involved in the interaction are depicted in the TM helices. Interaction of Vpu’s CT with the E3 ubiquitin (Ub) ligase via the βTrCP subunit is required for Vpu-induced tetherin down-regulation.