Fig. 7
From: Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3
Architecture of the CD4/Nef/AP2 complex at the plasma membrane. a Structural model of the CD4/Nef/AP2 complex embedded in a dioleoyl model membrane. CD4 (orange) contains an extracellular immunoglobulin fold followed by a single transmembrane helix and the C-terminal cytoplasmic ___domain. Nef (wheat) interacts with the SQxxxLL motif of CD4 at the plasma membrane and contacts with the ExxxLL motif in its C-terminal flexible loop the α/σ2 subunits (blue) of the hetero-tetrameric AP2 complex. The protein complex is assembled from PDB accession codes 1WIO46, 2KLU47, 5NUI (this study), 3RBB38, 4NEE43 and 2XA744. b Close up of the two dileucine-based sorting motifs of CD4 (SQxxxLL, colored red) and Nef (ExxxLL, colored magenta) in the model of CD4/Nef/AP2 at the membrane. c Nef-mediated endocytosis involves a cascade of dileucine-based sorting motif interactions. Nef acts as an adapter bridging the endocytic sorting motifs of CD3 (YNELNL) and CD4 (SQIKRLL) to the α/σ2 subunits of the AP2 complex. AP2 in turn binds to clathrin via the LLNL motif in the hinge region of its β subunit, thereby inducing the formation of clathrin-coated pits and receptor endocytosis
