The effects of Nef and Vpu on intracellular trafficking. Top: Nef alters multiple intracellular trafficking steps. The ExxxLL motif in Nef directs interactions with AP complexes. Golgi-endosome-related trafficking and designated residues in Nef are depicted in purple; PM endosome in orange; endosome-MVB in red. SFK indicates unidentified Src-family kinase. Full length Nef molecule with the interaction motifs represents a composite of two solution NMR structures, Protein Data Bank ID's 2NEF and 1QA5,146,147 assembled in PyMOL. Bottom: intracellular trafficking steps likely affected by Vpu. The cytosolic domain of Vpu with designated DpSGxxpS motif represents solution NMR structure 1VPU.148 In both panels, wide green arrows represent normal intracellular trafficking pathways; other-colored narrow arrows represent trafficking stimulated by HIV-1 Nef or Vpu. Cellular structures: CCV, clathrin-coated vesicles; NCV, non-clathrin vesicles; SE, sorting endosome; MVB, multivesicular body; ERC, endosomal recycling center; RE, recycling endosomes; SV, secretory vesicles. Two structures involved in protein-degradation, proteosomes and lysosomes, are depicted in yellow.