PDBsum entry: 1hvo

Viral protein/DNA

PDB id: 1hvo

Contents

Protein chain

18 a.a.

DNA/RNA

Metals

_ZN

PDB id:

1hvo

Name:

Viral protein/DNA

Title:

Zinc-and sequence-dependent binding to nucleic acids by the n-terminal zinc finger domain of the HIV-1 nucleocapsid protein: nmr structure of the complex with the psi-site analog, d/acgcc

Structure:

DNA (5'-d(p Ap Cp Gp Cp C)-3'). Chain: d. Engineered: yes. HIV-1 nucleocapsid zinc finger. Chain: e. Engineered: yes

Source:

Synthetic: yes. Human immunodeficiency virus 1. Organism_taxid: 11676

NMR struc:

15 models

Authors:

T.L.South,M.F.Summers

Key ref:

T.L.South and M.F.Summers (1993). Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC. Protein Sci, 2, 3. PubMed id: 8443588 Ref: Full text

Date:

08-Dec-92 Release date: 31-Jan-94

Protein chain

Q70622  (GAG_HV1LW) -  Gag polyprotein

Seq: 500 a.a.

Struc: 18 a.a.

 Gene Ontology (GO) functional annotation 

• Biochemical function: nucleic acid binding (2 terms)

Full text	Protein Sci 2:3 (1993)
PubMed id: 8443588

Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC.

T.L.South, M.F.Summers.

ABSTRACT

The nucleic acid interactive properties of a synthetic peptide with sequence of the N-terminal CCHC zinc finger (CCHC = Cys-X2-Cys-X4-His-X4-Cys; X = variable amino acid) of the human immunodeficiency virus (HIV) nucleocapsid protein, Zn(HIV1-F1), have been studied by 1H NMR spectroscopy. Titration of Zn(HIV1-F1) with oligodeoxyribonucleic acids containing different nucleotide sequences reveals, for the first time, sequence-dependent binding that requires the presence of at least one guanosine residue for tight complex formation. The dynamics of complex formation are sensitive to the nature of the residues adjacent to guanosine, with residues on the 3' side of guanosine having the largest influence. An oligodeoxyribonucleotide with sequence corresponding to a portion of the HIV-1 psi-packaging signal, d(ACGCC), forms a relatively tight complex with Zn(HIV1-F1) (Kd = 5 x 10(-6) M). Two-dimensional nuclear Overhauser effect (NOESY) data indicate that the bound nucleic acid exists predominantly in a single-stranded, A-helical conformation, and the presence of more than a dozen intermolecular NOE cross peaks enabled three-dimensional modeling of the complex. The nucleic acid binds within a hydrophobic cleft on the peptide surface. This hydrophobic cleft is defined by the side chains of residues Val1, Phe4, Ile12, and Ala13. Backbone amide protons of Phe4 and Ala13 and the backbone carbonyl oxygen of Lys2 that lie within this cleft appear to form hydrogen bonds with the guanosine O6 and N1H atoms, respectively. In addition, the positively charged side chain of Arg14 is ideally positioned for electrostatic interactions with the phosphodiester backbone of the nucleic acid. The structural findings provide a rationalization for the general conservation of these hydrophobic and basic residues in CCHC zinc fingers, and are consistent with site-directed mutagenesis results that implicate these residues as direct participants in viral genome recognition.

Selected figure(s)

Figure 10.
Fig. 10. Stereorawin of arepre- sentative Zn(HIV1-Fl):d(ACGCC) structure (peptide backbone in blue and nucleic acid in redshowing the topology of more prominent in- ermolecular NOEs observed Cgreen).

Figure 12.
Wig. 12. Space-fiing representation ofZn(HIV1-F1)shoing the hy- drophobic left byconservatively substitutedVal', Phe4, and Alag3 residues (the nucleicacidhs been removed clarity). ithinthiscleft, the backboneamidesof Phe4 and la,and the car- onyloxygen of are poised to form hydrogen bonds to h 3. Sidechains are coloredaccording to theShapelymodelcoloringscheme (blue,basic;green,hydrophobic; red, acidic). figure as generated withRASTE3D software.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1993, 2, 3-0) copyright 1993.

Figures were selected by an automated process.