The N-terminal Arg-rich region of human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus Nef is involved in RNA binding.
Comparison of the amino acid sequences of human immunodeficiency virus (HIV) Nef protein and several RNA-binding proteins shows similarities in some regions of these proteins. Thus, poliovirus protein 2C, an RNA-binding protein, shares with Nef the sequence YXQQ...MDD...DXXD. In addition, both proteins contain an Arg-rich motif that, in the case of poliovirus 2C, is involved in RNA-binding activity. Moreover, the RNA-binding, anti-terminator N proteins of lambda, phi21 and P22 phages show sequence similarities with HIV Nef at the Arg-rich motif. To assess the significance of this motif, native and deletion variants of Nef protein were assayed for RNA-binding activity. The N-terminal 35 amino acids of HIV-1 Nef that comprise the Arg-rich motif are sufficient for RNA binding. Point mutations engineered at the Arg-rich motif of HIV-1 Nef revealed that basic amino acid residues are essential for RNA-binding activity. The Nef proteins from HIV-2 and SIV can also interact with RNA, while the same proteins with the N-terminal Arg-rich domain truncated fail to interact with RNA. These findings indicate that all three Nef proteins from HIV-1, HIV-2 and simian immunodeficiency virus belong to the RNA-binding family of proteins. The three proteins contain an Arg-rich region at the N-terminus which is necessary to interact with RNA.
Echarri
A
A
Centro de Biología Molecular CSIC-UAM, Universidad Autónoma de Madrid, Spain.
González
M E
ME
Carrasco
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L
D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D015693:Gene Products, nef / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D015498:HIV-2 / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D012313:RNA / Q000378:metabolism*; D015347:RNA Probes; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D015302:Simian Immunodeficiency Virus / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015347:RNA Probes; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D012313:RNA; D001120:Arginine