PDBsum entry: 1bj6

Viral protein/DNA

PDB id: 1bj6

Contents

Protein chain

42 a.a. *

DNA/RNA

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

1bj6

Name:

Viral protein/DNA

Title:

1h nmr of (12-53) ncp7/d(acgcc) complex, 10 structures

Structure:

DNA (5'-d( Ap Cp Gp Cp C)-3'). Chain: d. Engineered: yes. Nucleocapsid protein 7. Chain: a. Fragment: residues 12-53. Synonym: (12-53)ncp7. Engineered: yes

Source:

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

NMR struc:

10 models

Authors:

H.Demene,N.Morellet,V.Teilleux,T.Huynh-Dinh,H.De Rocquigny, M.C.Fournie-Zaluski,B.P.Roques

Key ref:

N.Morellet et al. (1998). Structure of the complex between the HIV-1 nucleocapsid protein NCp7 and the single-stranded pentanucleotide d(ACGCC). J Mol Biol, 283, 419-434. PubMed id: 9769215 DOI: 10.1006/jmbi.1998.2098

Date:

03-Jul-98 Release date: 02-Feb-99

Protein chain

Q74084  (Q74084_9HIV1) -  Gag

Seq: 512 a.a.

Struc: 42 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Biochemical function: nucleic acid binding (2 terms)

DOI no: 10.1006/jmbi.1998.2098

J Mol Biol 283:419-434 (1998)

PubMed id: 9769215

Structure of the complex between the HIV-1 nucleocapsid protein NCp7 and the single-stranded pentanucleotide d(ACGCC).

N.Morellet, H.Déméné, V.Teilleux, T.Huynh-Dinh, H.de Rocquigny, M.C.Fournié-Zaluski, B.P.Roques.

ABSTRACT

The nucleocapsid protein NCp7 of HIV-1 Mal contains two successive Zn knuckles of the CX2CX4HX4C type and plays a major role in virion morphogenesis, genomic RNA packaging and viral infectivity, mainly through single-stranded nucleic acid binding. We report here the study by 1H 2D NMR of the complex formed between the (12-53)NCp7, encompassing the two Zn knuckles, and d(ACGCC), a deoxynucleotide sequence analog corresponding to the shortest NCp7 binding site. Ten structures of the (12-53)NCp7/d(ACGCC) complex have been obtained from 607 NOE-derived distance constraints, 28 of which are intermolecular, and from molecular dynamics studies. The oligonucleotide is almost perpendicular to the sequence linking the two Zn knuckles. The Trp37 indole ring is inserted between the C2 and G3 bases and stacked on the latter. The complex is stabilized by hydrophobic interactions and hydrogen bonds, and accounts for the observed loss of virus infectivity induced by mutations in the Zn knuckle domain. Thus, the interaction between d(ACGCC) and the inactive mutant Cys23 (12-53)NCp7 was found by NMR to be completely different from that observed with the wild-type peptide. A mechanism of action for NCp7 in virus morphogenesis and replication is proposed from these results, which could facilitate the design of possible antiviral agents acting by a new mechanism.

Selected figure(s)

Figure 1.
Figure 1. Sequence of the HIV-1 nucleocapsid protein NCp7.

Figure 10.
Figure 10. Comparison of the (12-53)NCp7/d(ACGCC) and (1-55)NCp7/SL3 (de Guzman et al., 1998) complexes after superposition of the (36-49)NCp7 domain. Only the set of residues that is implicated in the interactions is rep- resented: the hydrophobic residues (Val13, Thr24, Ala25, Gln45 and Met46) and the residues implicated in electro- static interactions (Arg26, Arg32 and Lys47) are in pink, Phe16 and Trp37 are in red, and the nucleic acids are in blue. The structures show the stacking of Trp37 with the guanine residues.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 283, 419-434) copyright 1998.

Figures were selected by an automated process.