CD8:Nef:AP-2 Complex:v-ATPase Complex CD8:Nef Complex AP-2 Complex Formation of CD8:Nef:AP-2 Complex:v-ATPase Complex Authored: Gillespie, ME, 2007-07-25 19:42:36 Pubmed16103193 Reactome Database ID Release 43182186 Reactome, http://www.reactome.org ReactomeREACT_11125 Reviewed: Skowronski, J, 2007-08-07 14:33:41 The presence of Nef accelerates endocytosis and lysosomal degradation of the transmembrane glycoprotein CD8. Nef facilitates a cascade of protein interactions that ultimately result in the degradation of internalized CD8 protein. The final set of protein interactions that direct Nef to the beta-subunit of the COPI coatomers are at this time unclear.<br>A number of sites within Nef are proposed to be required for CD8 down-regulation, the myristoylation signal and N-terminal anchor regions, the C-terminal flexible loop, and amino acid positions 57 to 58. Consistent with all reported Nef functions, the myristoylation signal was found to be essential for CD8 down-modulation. The flexible loop contains a dileucine-based internalization motif, which is flanked by acidic clusters and is involved in enhanced internalization of the Nef-CD4 complex.