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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. 1991

K P Samuel, and D R Hodge, and Y M Chen, and T S Papas
Laboratory of Cellular Biochemistry, Program Resources, Inc./DynCorp, Frederick, MD.

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.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D015302 Simian Immunodeficiency Virus Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV. SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015498 HIV-2 An HIV species related to HIV-1 but carrying different antigenic components and with differing nucleic acid composition. It shares serologic reactivity and sequence homology with the simian Lentivirus SIMIAN IMMUNODEFICIENCY VIRUS and infects only T4-lymphocytes expressing the CD4 phenotypic marker. HTLV-IV,Human T-Lymphotropic Virus Type IV,Human immunodeficiency virus 2,LAV-2,HIV-II,Human Immunodeficiency Virus Type 2,Human T Lymphotropic Virus Type IV,Immunodeficiency Virus Type 2, Human,SBL-6669
D015534 Trans-Activators Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins. Nuclear Trans-Acting Factor,Trans-Acting Factors,Trans-Acting Factor,Trans-Activator,Transactivator,Transactivators,Factor, Nuclear Trans-Acting,Factor, Trans-Acting,Factors, Trans-Acting,Nuclear Trans Acting Factor,Trans Acting Factor,Trans Acting Factors,Trans Activator,Trans Activators,Trans-Acting Factor, Nuclear
D015693 Gene Products, nef Products of the retroviral NEF GENE. They play a role as accessory proteins that influence the rate of viral infectivity and the destruction of the host immune system. nef gene products were originally found as factors that trans-suppress viral replication and function as negative regulators of transcription. nef stands for negative factor. nef Gene Products,nef Protein,3'-orf Protein,Gene Product, nef,3' orf Protein,nef Gene Product
D016350 Leucine Zippers DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y. Leucine Zipper,Zipper, Leucine,Zippers, Leucine
D016415 Sequence Alignment The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations
D054311 nef Gene Products, Human Immunodeficiency Virus Proteins encoded by the NEF GENES of the HUMAN IMMUNODEFICIENCY VIRUS. nef Protein, Human Immunodeficiency Virus,HIV-3'-orf Protein,nef Protein, HIV,HIV 3' orf Protein,HIV nef Protein

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