PDBsum entry: 1hvn

Viral protein/DNA

PDB-id

1hvn


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Protein chain

DNA/RNA

Metal ions

_ZN

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PDB id:

1hvn

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

UniProt:

Q70622 (GAG_HV1LW)

Seq:

Struc:

Seq:

500 a.a.

Struc:

18 a.a.

Key:

PfamA domain

Secondary structure

Resolution:

not givenÅ

NMR structure:

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]

Date:

08-Dec-92

Release date:

31-Jan-94

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Key reference

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.

Literature references that cite this PDB file's key reference

PubMed id Reference

19039000 D.Sela, and J.Shlomai (2009).
Regulation of UMSBP activities through redox-sensitive protein domains.

Nucleic Acids Res, 37, 279-288.

18971263 T.T.Baig, J.M.Lanchy, and J.S.Lodmell (2009).
Randomization and in vivo selection reveal a GGRG motif essential for packaging human immunodeficiency virus type 2 RNA.

J Virol, 83, 802-810.

18684831 K.M.Stewart-Maynard, M.Cruceanu, F.Wang, M.N.Vo, R.J.Gorelick, M.C.Williams, I.Rouzina, and K.Musier-Forsyth (2008).
Retroviral nucleocapsid proteins display nonequivalent levels of nucleic acid chaperone activity.

J Virol, 82, 10129-10142.

17265140 E.Burkala, and M.Poss (2007).
Evolution of feline immunodeficiency virus Gag proteins.

Virus Genes, 35, 251-264.

17070546 J.Zhou, R.L.Bean, V.M.Vogt, and M.Summers (2007).
Solution structure of the Rous sarcoma virus nucleocapsid protein: muPsi RNA packaging signal complex.

J Mol Biol, 365, 453-467.

PDB code: 2ihx

17553835 T.Wu, S.L.Heilman-Miller, and J.G.Levin (2007).
Effects of nucleic acid local structure and magnesium ions on minus-strand transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid protein.

Nucleic Acids Res, 35, 3974-3987.

16064056 V.D'Souza, and M.F.Summers (2005).
How retroviruses select their genomes.

Nat Rev Microbiol, 3, 643-655.

15075258 I.Onn, N.Milman-Shtepel, and J.Shlomai (2004).
Redox potential regulates binding of universal minicircle sequence binding protein at the kinetoplast DNA replication origin.

Eukaryot Cell, 3, 277-287.

15345057 R.S.Russell, C.Liang, and M.A.Wainberg (2004).
Is HIV-1 RNA dimerization a prerequisite for packaging? Yes, no, probably?

Retrovirology, 1, 23.

10982342 J.Guo, T.Wu, J.Anderson, B.F.Kane, D.G.Johnson, R.J.Gorelick, L.E.Henderson, and J.G.Levin (2000).
Zinc finger structures in the human immunodeficiency virus type 1 nucleocapsid protein facilitate efficient minus- and plus-strand transfer.

J Virol, 74, 8980-8988.

10924101 P.E.Johnson, R.B.Turner, Z.R.Wu, L.Hairston, J.Guo, J.G.Levin, and M.F.Summers (2000).
A mechanism for plus-strand transfer enhancement by the HIV-1 nucleocapsid protein during reverse transcription.

Biochemistry, 39, 9084-9091.

PDB code: 1en1

10606514 C.Vuilleumier, E.Bombarda, N.Morellet, D.Gérard, B.P.Roques, and Y.Mély (1999).
Nucleic acid sequence discrimination by the HIV-1 nucleocapsid protein NCp7: a fluorescence study.

Biochemistry, 38, 16816-16825.

9618469 A.Y.Louie, and T.J.Meade (1998).
A cobalt complex that selectively disrupts the structure and function of zinc fingers.

Proc Natl Acad Sci U S A, 95, 6663-6668.

10333745 R.N.De Guzman, R.B.Turner, and M.F.Summers (1998).
Protein-RNA recognition.

Biopolymers, 48, 181-195.

9501077 U.K.von Schwedler, T.L.Stemmler, V.Y.Klishko, S.Li, K.H.Albertine, D.R.Davis, and W.I.Sundquist (1998).
Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly.

EMBO J, 17, 1555-1568.

9827993 Y.Gao, K.Kaluarachchi, and D.P.Giedroc (1998).
Solution structure and backbone dynamics of Mason-Pfizer monkey virus (MPMV) nucleocapsid protein.

Protein Sci, 7, 2265-2280.

PDB code: 1cl4

9223458 N.Sheng, S.C.Pettit, R.J.Tritch, D.H.Ozturk, M.M.Rayner, R.Swanstrom, and S.Erickson-Viitanen (1997).
Determinants of the human immunodeficiency virus type 1 p15NC-RNA interaction that affect enhanced cleavage by the viral protease.

J Virol, 71, 5723-5732.

8551614 E.Schmalzbauer, B.Strack, J.Dannull, S.Guehmann, and K.Moelling (1996).
Mutations of basic amino acids of NCp7 of human immunodeficiency virus type 1 affect RNA binding in vitro.

J Virol, 70, 771-777.

8551627 J.F.Kaye, and A.M.Lever (1996).
trans-acting proteins involved in RNA encapsidation and viral assembly in human immunodeficiency virus type 1.

J Virol, 70, 880-886.

8551604 K.de Vreese, V.Kofler-Mongold, C.Leutgeb, V.Weber, K.Vermeire, S.Schacht, J.Anné, E.de Clercq, R.Datema, and G.Werner (1996).
The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication.

J Virol, 70, 689-696.

8836184 R.Khan, H.O.Chang, K.Kaluarachchi, and D.P.Giedroc (1996).
Interaction of retroviral nucleocapsid proteins with transfer RNAPhe: a lead ribozyme and 1H NMR study.

Nucleic Acids Res, 24, 3568-3575.

8755517 Y.X.Feng, T.D.Copeland, L.E.Henderson, R.J.Gorelick, W.J.Bosche, J.G.Levin, and A.Rein (1996).
HIV-1 nucleocapsid protein induces "maturation" of dimeric retroviral RNA in vitro.

Proc Natl Acad Sci U S A, 93, 7577-7581.

7884856 J.Clever, C.Sassetti, and T.G.Parslow (1995).
RNA secondary structure and binding sites for gag gene products in the 5' packaging signal of human immunodeficiency virus type 1.

J Virol, 69, 2101-2109.

8083960 N.Sheng, and S.Erickson-Viitanen (1994).
Cleavage of p15 protein in vitro by human immunodeficiency virus type 1 protease is RNA dependent.

J Virol, 68, 6207-6214.

8510214 R.J.Gorelick, D.J.Chabot, A.Rein, L.E.Henderson, and L.O.Arthur (1993).
The two zinc fingers in the human immunodeficiency virus type 1 nucleocapsid protein are not functionally equivalent.

J Virol, 67, 4027-4036.

8371356 T.Dorfman, J.Luban, S.P.Goff, W.A.Haseltine, and H.G.Göttlinger (1993).
Mapping of functionally important residues of a cysteine-histidine box in the human immunodeficiency virus type 1 nucleocapsid protein.

J Virol, 67, 6159-6169.

7692451 W.G.Rice, C.A.Schaeffer, L.Graham, M.Bu, J.S.McDougal, S.L.Orloff, F.Villinger, M.Young, S.Oroszlan, and M.R.Fesen (1993).
The site of antiviral action of 3-nitrosobenzamide on the infectivity process of human immunodeficiency virus in human lymphocytes.

Proc Natl Acad Sci U S A, 90, 9721-9724.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.