Figure 6.

Model: Requirement of motifs in SIV_mac239 Nef for its internalization and viral infectivity. (A) Shown is the interaction of the C-terminal flexible loop of Nef with V1H. Both the L₁₉₄M₁₉₅ and D₂₀₄D₂₀₅ and to a lesser degree the D₁₈₄E₁₈₅ motifs are required for the binding to V1H, which then binds to AP-2. AP-2 also binds directly to the first tyrosine-based motif (Y₂₈GRL). AP-2 binds to clathrin and V1H binds to and is part of the V-ATPase. Both loop motifs (L₁₉₄M₁₉₅ and D₂₀₄D₂₀₅) and the second tyrosine-based motif (Y₃₉SQS) are required for optimal viral infectivity. (B) Shown is the trafficking route of the V-ATPase in the cell (modified from Stevens and Forgac, 1997). It is similar to trafficking routes of Nef. The exocytic (left side) and endocytic (right side) pathways are highlighted for clarity. On the right side is the route of the V-ATPase from the plasma membrane to early endosomes (1), late endosomes (2), and lysosomes (3). The V-ATPase also trafficks in the exocytic route from the TGN directly (6) or indirectly via the endosomal compartment (4 and 5) to the plasma membrane (CCP, clathrin-coated pit; CCV, clathrin coated vesicle; m, myristate; PM, plasma membrane; TGN, trans-Golgi network).