Nef proteins of the human immunodeficiency viruses (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV) are structurally similar to leucine zipper transcriptional activation factors.
Analysis of the predicted amino acid sequences of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and of the related simian immunodeficiency virus (SIV) nef gene products (Nef) reveals the presence of a conserved leucine zipper-like repeat with the characteristic 4,3 arrangement of mainly hydrophobic amino acids in the middle (core) region of the proteins, but lacking the basic (DNA binding) domain characteristic of DNA-binding leucine zipper (bZIP) proteins. Also, at the C-terminus of the Nef proteins is a highly acidic sequence (net charge of -5 to -8) stretched over about 40 amino acids, and contains two predicted alpha-helices separated by a beta-turn linker sequence with sequence homology to known activation domains of acidic transcriptional activation factors. Moreover, within this acidic region of transcriptional activators and the homologous sequence within the second Nef alpha-helix, is a potential transcriptional activation consensus sequence (TACS) bounded by a pair of acidic amino acids (aspartic or glutamic acids) at the N-terminus and a highly invariant phenylalanine (hydrophobic), often followed by an acidic (aspartic) residue, at the C-terminus of the sequence. These findings strongly implicate Nef proteins as belonging to a class of non-DNA-binding leucine zipper acidic transcription factors, and provide a structural basis for new approaches to studying Nef function.
Laboratory of Cellular Biochemistry, Program Resources, Inc./DynCorp, Frederick, MD.
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Samuel
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Hodge
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Chen
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Papas
D000595:Amino Acid Sequence; D015693:Gene Products, nef / Q000737:chemistry*; D015497:HIV-1; D015498:HIV-2; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus; D015534:Trans-Activators / Q000737:chemistry*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015534:Trans-Activators; D054311:nef Gene Products, Human Immunodeficiency Virus