1AAF

NUCLEOCAPSID ZINC FINGERS DETECTED IN RETROVIRUSES: EXAFS STUDIES ON INTACT VIRUSES AND THE SOLUTION-STATE STRUCTURE OF THE NUCLEOCAPSID PROTEIN FROM HIV-1

Summary for 1AAF

• Entry DOI: 10.2210/pdb1aaf/pdb
• Descriptor: HIV-1 NUCLEOCAPSID PROTEIN, ZINC ION (2 entities in total)
• Functional Keywords: viral protein
• Biological source: Human immunodeficiency virus 1
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P05961
• Total number of polymer chains: 1
• Total formula weight: 6599.42

Authors

Summers, M.F.,Henderson, L.E.,Chance, M.R.,Bess Junior, J.W.,South, T.L.,Blake, P.R.,Sagi, I.,Perez-Alvarado, G.,Sowder, R.C.,Hare, D.R.,Arthur, L.O. (deposition date: 1992-04-06, release date: 1994-01-31, Last modification date: 2024-04-10)

Primary citation

Summers, M.F.,Henderson, L.E.,Chance, M.R.,Bess Jr., J.W.,South, T.L.,Blake, P.R.,Sagi, I.,Perez-Alvarado, G.,Sowder 3rd., R.C.,Hare, D.R.,Arthur, L.O.
Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution-state structure of the nucleocapsid protein from HIV-1.
Protein Sci., 1:563-574, 1992

PubMed Abstract: All retroviral nucleocapsid (NC) proteins contain one or two copies of an invariant 3Cys-1His array (CCHC = C-X2-C-X4-H-X4-C; C = Cys, H = His, X = variable amino acid) that are essential for RNA genome packaging and infectivity and have been proposed to function as zinc-binding domains. Although the arrays are capable of binding zinc in vitro, the physiological relevance of zinc coordination has not been firmly established. We have obtained zinc-edge extended X-ray absorption fine structure (EXAFS) spectra for intact retroviruses in order to determine if virus-bound zinc, which is present in quantities nearly stoichiometric with the CCHC arrays (Bess, J.W., Jr., Powell, P.J., Issaq, H.J., Schumack, L.J., Grimes, M.K., Henderson, L.E., & Arthur, L.O., 1992, J. Virol. 66, 840-847), exists in a unique coordination environment. The viral EXAFS spectra obtained are remarkably similar to the spectrum of a model CCHC zinc finger peptide with known 3Cys-1His zinc coordination structure. This finding, combined with other biochemical results, indicates that the majority of the viral zinc is coordinated to the NC CCHC arrays in mature retroviruses. Based on these findings, we have extended our NMR studies of the HIV-1 NC protein and have determined its three-dimensional solution-state structure. The CCHC arrays of HIV-1 NC exist as independently folded, noninteracting domains on a flexible polypeptide chain, with conservatively substituted aromatic residues forming hydrophobic patches on the zinc finger surfaces. These residues are essential for RNA genome recognition, and fluorescence measurements indicate that at least one residue (Trp37) participates directly in binding to nucleic acids in vitro. The NC is only the third HIV-1 protein to be structurally characterized, and the combined EXAFS, structural, and nucleic acid-binding results provide a basis for the rational design of new NC-targeted antiviral agents and vaccines for the control of AIDS.

PubMed: 1304355

Experimental method

SOLUTION NMR