Domain assembly, surface accessibility and sequence conservation in full length HIV-1 Nef.

The accessory Nef protein from human and simian immunodeficiency viruses is critical for efficient viral replication and pathogenesis. Here we present an assembly of the full length structure of HIV-1 Nef, allele NL4-3, based on the previously solved anchor and core domain structures. The center part of the 33 residue encompassing flexible loop at the C-terminus of Nef, involved in Nef internalization and CD4 endocytosis, has been modelled. The degree of sequence conservation in HIV-1 Nef proteins was determined using a total of 186 different strains from five different subtypes. The sequence conservation has been correlated with the accessible surface area and with secondary structure features for individual residues. The high amount of flexible regions in Nef accounts for the large surface and the multiple interaction sites the protein exhibits.