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. 2016 Mar 3;8(3):67. doi: 10.3390/v8030067

Figure 1.

Figure 1

Structure of human immunodeficiency virus type I (HIV-1) negative factor (Nef) protein and viral protein U (Vpu). (A) HIV-1 Nef is a soluble protein found associated with cellular membranes through a myristate moiety added post-translationally to a glycine residue at amino acid (aa) position 2. Nef is composed of a compact globular core region (aa 58–149, 181–206) a flexible N-terminus (aa 1–57) and a C-terminal loop (aa 150–180). Conserved motifs of Nef include an adaptor protein (AP)-1/2-binding di-leucine sorting signal and a coatomer subunit beta (β-COP)-binding di-acidic motif both found within the C-terminal loop (aa 160-ExxxLL-165 and 155-EE-156, respectively), a Src family kinase (SFK)-binding polyproline domain (aa 72-PxxP-75) found within the core, and a phosphofurin acid cluster sorting proteins (PACS)-binding acidic cluster (aa 62-EEEE-65) in the N-terminal region; (B) HIV-1 Vpu is a transmembrane (TM) protein comprised of a 4 aa luminal tail, a single α-helical TM domain and a cytosolic domain that includes a flexible linker region and two α-helices (H1 and H2) flanking a conserved dual serine motif (aa 51-DSGxxS-56). The dual serine motif of Vpu is readily phosphorylated by casein kinase-2 (CK-II), promoting the recruitment of the beta-transducin repeats-containing proteins (β-TrCP) component of the Skp, Cullin, F-box-containing (SCF)β−TrCP E3 ubiquitin ligase complex. An AP-1/2-interacting sorting motif (aa 59-ExxxLV-64) is found in the second α-helix of the cytoplasmic domain of most group M Vpus. Numbering of aa is based on the Vpu and Nef proteins from the prototypical pNL4-3 molecular clone of HIV-1.