Structure of the zinc finger domain encompassing residues 13-51 of the nucleocapsid protein from simian immunodeficiency virus.
The NCps (nucleocapsid proteins) of HIV-1 (HIV type 1), HIV-2 and SIV (simian immunodeficiency virus) are small highly basic proteins, characterized by the presence of two CCHC ZF (zinc finger) domains. NCps, closely associated with the dimeric RNA genome in the core of the virus particle, were shown to promote the specific encapsidation of the viral RNA and are implicated in reverse transcription. Solution structure of the HIV-1 NCp7 and complexes of NCp7 with RNA or DNA showed the critical relationships between the structure and its various functions. HIV-1 and HIV-2 have resulted respectively from transmissions of SIV from chimpanzees and sooty mangabeys. It has been shown that the SIVlhoest (SIV from l'Hoest monkeys) also has the potential to infect human populations. Since monkeys are of great interest for clinical studies of antiviral drugs, the structure of (13-51)NCp8 (zinc finger domain of NCp8, encompassing residues 13-51) from SIVlhoest was determined by NMR to appraise the influence of major differences in the sequence, since Glu21, Gly43 and Met46 in NCp7 are replaced by Pro, Glu and Phe respectively in this particular NCp8. The structure of (13-51)NCp8 is very well defined, and surprisingly the structure of each ZF is similar in NCp7 and NCp8. Moreover, contrary to NCp7, the two ZFs are strongly locked to each other in this NCp8. This first reported structure of a simian NCp8 compared with that of NCp7 shows that the main structural differences occur at the flexible linker between the two ZFs but the essential residues responsible for the interaction with oligonucleotides adopt the same orientation in the two proteins.
Morellet
Nelly
N
Unité de Pharmacologie Chimique et Génétique, INSERM U640-CNRS UMR 8151, UFR des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75270 Paris cedex 06, France. morellet@pharmacie.univ-paris5.fr
Meudal
Hervé
H
Bouaziz
Serge
S
Roques
Bernard Pierre
BP
D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry*; D015683:Gene Products, gag / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry; D016335:Zinc Fingers; D054301:gag Gene Products, Human Immunodeficiency Virus
D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D015683:Gene Products, gag; C071884:NCP7 protein, Human immunodeficiency virus 1; D019590:Nucleocapsid Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C407345:nucleocapsid protein 8, SIV