A cooperative and specific DNA-binding mode of HIV-1 integrase depends on the nature of the metallic cofactor and involves the zinc-containing N-terminal domain

Nucleic Acids Research

Volumn 38, Issue 11, 2010, Pages 3692-3708

  Carayon, Kevin ^a   leh, Hervé ^a   Henry, Etienne ^a   Simon, Françoise ^a   Mouscadet, Jean François ^a   Deprez, Eric ^a  

^a Ecole Normale Superieure de Cachan   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2,2' DITHIOBISBENZAMIDE 1; BENZAMIDE DERIVATIVE; CYSTEINE; INTEGRASE; MAGNESIUM; MANGANESE; OLIGOMER; UNCLASSIFIED DRUG; VIRUS DNA; ZINC; ZINC FINGER PROTEIN;

3' UNTRANSLATED REGION; AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; CATALYSIS; CONTROLLED STUDY; COVALENT BOND; DNA SEQUENCE; ENZYME SPECIFICITY; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN DOMAIN; PROTEIN MOTIF; PROTEIN PROCESSING;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77954381613     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkq087     Document Type: Article

References (68)

1. Delelis, O., Carayon, K., Saib, A., Deprez, E. and Mouscadet, J.F. (2008) Integrase and integration: biochemical activities of HIV-1 integrase. Retrovirology, 5, 114.
2. Faure, A., Calmels, C., Desjobert, C., Castroviejo, M., Caumont-Sarcos, A., Tarrago-Litvak, L., Litvak, S. and Parissi, V. (2005) HIV-1 integrase crosslinked oligomers are active in vitro. Nucleic Acids Res., 33, 977-986.
3. Guiot, E., Carayon, K., Delelis, O., Simon, F., Tauc, P., Zubin, E., Gottikh, M., Mouscadet, J.F., Brochon, J.C. and Deprez, E. (2006) Relationship between the oligomeric status of HIV-1 integrase on DNA and enzymatic activity. J. Biol. Chem., 281, 22707-22719.
4. Li, M., Mizuuchi, M., Burke, T.R. Jr and Craigie, R. (2006) Retroviral DNA integration: reaction pathway and critical intermediates. EMBO J., 25, 1295-1304.
5. Delelis, O., Carayon, K., Guiot, E., Leh, H., Tauc, P., Brochon, J.C., Mouscadet, J.F. and Deprez, E. (2008) Insight into the integrase-DNA recognition mechanism. A specific DNA-binding mode revealed by an enzymatically labeled integrase. J. Biol. Chem., 283, 27838-27849.
6. Baranova, S., Tuzikov, F.V., Zakharova, O.D., Tuzikova, N.A., Calmels, C., Litvak, S., Tarrago-Litvak, L., Parissi, V. and Nevinsky, G.A. (2007) Small-angle X-ray characterization of the nucleoprotein complexes resulting from DNA-induced oligomerization of HIV-1 integrase. Nucleic Acids Res., 35, 975-987.
7. Hare, S., Shree Gupta, S., Valkov, E., Engelman, A. and Cherepanov, P. (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. Nature, [Epub ahead of print; doi:10.1038/nature08784; 31 January 2010].
8. Chow, S.A., Vincent, K.A., Ellison, V. and Brown, P.O. (1992) Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. Science, 255, 723-726.
9. Delelis, O., Parissi, V., Leh, H., Mbemba, G., Petit, C., Sonigo, P., Deprez, E. and Mouscadet, J.F. (2007) Efficient and specific internal cleavage of a retroviral palindromic DNA sequence by tetrameric HIV-1 integrase. PLoS.ONE., 2, e608.
10. Gerton, J.L. and Brown, P.O. (1997) The core domain of HIV-1 integrase recognizes key features of its DNA substrates. J. Biol. Chem., 272, 25809-25815.
11. Laboulais, C., Deprez, E., Leh, H., Mouscadet, J.F., Brochon, J.C. and Le Bret, M. (2001) HIV-1 integrase catalytic core: molecular dynamics and simulated fluorescence decays. Biophys. J., 81, 473-489.
12. Esposito, D. and Craigie, R. (1998) Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interaction. EMBO J., 17, 5832-5843.
13. Agapkina, J., Smolov, M., Barbe, S., Zubin, E., Zatsepin, T., Deprez, E., Le Bret, M., Mouscadet, J.F. and Gottikh, M. (2006) Probing of HIV-1 integrase/DNA interactions using novel analogs of viral DNA. J. Biol. Chem., 281, 11530-11540.
14. Skinner, L.M., Sudol, M., Harper, A.L. and Katzman, M. (2001) Nucleophile selection for the endonuclease activities of human, ovine, and avian retroviral integrases. J. Biol. Chem., 276, 114-124.
15. Engelman, A. and Craigie, R. (1995) Efficient magnesium-dependent human immunodeficiency virus type 1 integrase activity. J. Virol., 69, 5908-5911.
16. Semenova, E.A., Marchand, C. and Pommier, Y. (2008) HIV-1 integrase inhibitors: update and perspectives. Adv. Pharmacol., 56, 199-228.
17. Bonnenfant, S., Thomas, C.M., Vita, C., Subra, F., Deprez, E., Zouhiri, F., Desmaele, D., d'Angelo, J., Mouscadet, J.F. and Leh, H. (2004) Styrylquinolines, integrase inhibitors acting prior to integration: a new mechanism of action for anti-integrase agents. J. Virol., 78, 5728-5736.
18. Deprez, E., Barbe, S., Kolaski, M., Leh, H., Zouhiri, F., Auclair, C., Brochon, J.C., Le Bret, M. and Mouscadet, J.F. (2004) Mechanism of HIV-1 integrase inhibition by styrylquinoline derivatives in vitro. Mol. Pharmacol., 65, 85-98.
19. Espeseth, A.S., Felock, P., Wolfe, A., Witmer, M., Grobler, J., Anthony, N., Egbertson, M., Melamed, J.Y., Young, S., Hamill, T. et al. (2000) HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase. Proc. Natl Acad. Sci. USA, 97, 11244-11249.
20. Hazuda, D.J., Felock, P., Witmer, M., Wolfe, A., Stillmock, K., Grobler, J.A., Espeseth, A., Gabryelski, L., Schleif, W., Blau, C. et al. (2000) Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science, 287, 646-650.
21. Dicker, I.B., Samanta, H.K., Li, Z., Hong, Y., Tian, Y., Banville, J., Remillard, R.R., Walker, M.A., Langley, D.R. and Krystal, M. (2007) Changes to the HIV long terminal repeat and to HIV integrase differentially impact HIV integrase assembly, activity, and the binding of strand transfer inhibitors. J. Biol. Chem., 282, 31186-31196.
22. Delelis, O., Malet, I., Na, L., Tchertanov, L., Calvez, V., Marcelin, A.G., Subra, F., Deprez, E. and Mouscadet, J.F. (2009) The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Nucleic Acids Res., 37, 1193-1201.
23. Delelis, O., Thierry, S., Subra, F., Simon, F., Malet, I., Alloui, C., Sayon, S., Calvez, V., Deprez, E., Marcelin, A.G. et al. (2010) Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. Antimicrob. Agents Chemother., 54, 491-501.
24. Yi, J., Asante-Appiah, E. and Skalka, A.M. (1999) Divalent cations stimulate preferential recognition of a viral DNA end by HIV-1 integrase. Biochemistry, 38, 8458-8468.
25. Engelman, A., Hickman, A.B. and Craigie, R. (1994) The core and carboxyl-terminal domains of the integrase protein of human immunodeficiency virus type 1 each contribute to nonspecific DNA binding. J. Virol., 68, 5911-5917.
26. Gao, K., Butler, S.L. and Bushman, F. (2001) Human immunodeficiency virus type 1 integrase: arrangement of protein domains in active cDNA complexes. EMBO J., 20, 3565-3576.
27. Deprez, E., Tauc, P., Leh, H., Mouscadet, J.F., Auclair, C. and Brochon, J.C. (2000) Oligomeric states of the HIV-1 integrase as measured by time-resolved fluorescence anisotropy. Biochemistry, 39, 9275-9284.
28. Zheng, R., Jenkins, T.M. and Craigie, R. (1996) Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity. Proc. Natl Acad. Sci. USA, 93, 13659-13664.
29. Lee, S.P., Xiao, J., Knutson, J.R., Lewis, M.S. and Han, M.K. (1997) Zn2+ promotes the self-association of human immunodeficiency virus type-1 integrase in vitro. Biochemistry, 36, 173-180.
30. Khan, E., Mack, J.P., Katz, R.A., Kulkosky, J. and Skalka, A.M. (1991) Retroviral integrase domains: DNA binding and the recognition of LTR sequences. Nucleic Acids Res., 19, 851-860.
31. Berthoux, L., Pechoux, C. and Darlix, J.L. (1999) Multiple effects of an anti-human immunodeficiency virus nucleocapsid inhibitor on virus morphology and replication. J. Virol., 73, 10000-10009.
32. Turpin, J.A., Terpening, S.J., Schaeffer, C.A., Yu, G., Glover, C.J., Felsted, R.L., Sausville, E.A. and Rice, W.G. (1996) Inhibitors of human immunodeficiency virus type 1 zinc fingers prevent normal processing of gag precursors and result in the release of noninfectious virus particles. J. Virol., 70, 6180-6189.
33. Rice, W.G., Supko, J.G., Malspeis, L., Buckheit, R.W. Jr, Clanton, D., Bu, M., Graham, L., Schaeffer, C.A., Turpin, J.A., Domagala, J. et al. (1995) Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS. Science, 270, 1194-1197.
34. Wang, L.H., Yang, X.Y., Zhang, X., Mihalic, K., Fan, Y.X., Xiao, W., Howard, O.M., Appella, E., Maynard, A.T. and Farrar, W.L. (2004) Suppression of breast cancer by chemical modulation of vulnerable zinc fingers in estrogen receptor. Nat. Med., 10, 40-47.
35. Bischerour, J., Leh, H., Deprez, E., Brochon, J.C. and Mouscadet, J.F. (2003) Disulfide-linked integrase oligomers involving C280 residues are formed in vitro and in vivo but are not essential for human immunodeficiency virus replication. J. Virol., 77, 135-141.
36. Pinskaya, M., Romanova, E., Volkov, E., Deprez, E., Leh, H., Brochon, J.C., Mouscadet, J.F. and Gottikh, M. (2004) HIV-1 integrase complexes with DNA dissociate in the presence of short oligonucleotides conjugated to acridine. Biochemistry, 43, 8735-8743.
37. Hunt, J.B., Neece, S.H., Schachman, H.K. and Ginsburg, A. (1984) Mercurial-promoted Zn2+ release from Escherichia coli aspartate transcarbamoylase. J. Biol. Chem., 259, 14793-14803.
38. Smolov, M., Gottikh, M., Tashlitskii, V., Korolev, S., Demidyuk, I., Brochon, J.C., Mouscadet, J.F. and Deprez, E. (2006) Kinetic study of the HIV-1 DNA 3′-end processing. FEBS J., 273, 1137-1151.
39. Anacona, J.R. and Gomez, J. (2008) Transition Metal Bis(2-Bromophenyl)disulfide complexes. J. Chil. Chem. Soc., 53, 1694-1696.
40. Zouhiri, F., Mouscadet, J.F., Mekouar, K., Desmaele, D., Savoure, D., Leh, H., Subra, F., Le Bret, M., Auclair, C. and d'Angelo, J. (2000) Structure-activity relationships and binding mode of styrylquinolines as potent inhibitors of HIV-1 integrase and replication of HIV-1 in cell culture. J. Med. Chem., 43, 1533-1540.
41. Loo, J.A., Holler, T.P., Sanchez, J., Gogliotti, R., Maloney, L. and Reily, M.D. (1996) Biophysical characterization of zinc ejection from HIV nucleocapsid protein by anti-HIV 2, 2′-dithiobis[benzamides] and benzisothiazolones. J. Med. Chem., 39, 4313-4320.
42. Ellison, V., Gerton, J., Vincent, K.A. and Brown, P.O. (1995) An essential interaction between distinct domains of HIV-1 integrase mediates assembly of the active multimer. J. Biol. Chem., 270, 3320-3326.
43. Johnson, A.A., Santos, W., Pais, G.C., Marchand, C., Amin, R., Burke, T.R. Jr, Verdine, G. and Pommier, Y. (2006) Integration requires a specific interaction of the donor DNA terminal 5′-cytosine with glutamine 148 of the HIV-1 integrase flexible loop. J. Biol. Chem., 281, 461-467.
44. Johnson, A.A., Marchand, C., Patil, S.S., Costi, R., Di Santo, R., Burke, T.R. Jr and Pommier, Y. (2007) Probing HIV-1 integrase inhibitor binding sites with position-specific integrase-DNA cross-linking assays. Mol. Pharmacol., 71, 893-901.
45. Grobler, J.A., Stillmock, K., Hu, B., Witmer, M., Felock, P., Espeseth, A.S., Wolfe, A., Egbertson, M., Bourgeois, M., Melamed, J. et al. (2002) Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc. Natl Acad. Sci. USA, 99, 6661-6666.
46. Leavitt, A.D., Robles, G., Alesandro, N. and Varmus, H.E. (1996) Human immunodeficiency virus type 1 integrase mutants retain in vitro integrase activity yet fail to integrate viral DNA efficiently during infection. J. Virol., 70, 721-728.
47. Wiskerchen, M. and Muesing, M.A. (1995) Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells. J. Virol., 69, 376-386.
48. Lee, S.P. and Han, M.K. (1996) Zinc stimulates Mg2+-dependent 3′-processing activity of human immunodeficiency virus type 1 integrase in vitro. Biochemistry, 35, 3837-3844.
49. Yang, F., Leon, O., Greenfield, N.J. and Roth, M.J. (1999) Functional interactions of the HHCC domain of moloney murine leukemia virus integrase revealed by nonoverlapping complementation and zinc-dependent dimerization. J. Virol., 73, 1809-1817.
50. Engelman, A., Bushman, F.D. and Craigie, R. (1993) Identification of discrete functional domains of HIV-1 integrase and their organization within an active multimeric complex. EMBO J., 12, 3269-3275.
51. Lesbats, P., Metifiot, M., Calmels, C., Baranova, S., Nevinsky, G., Andreola, M.L. and Parissi, V. (2008) In vitro initial attachment of HIV-1 integrase to viral ends: control of the DNA specific interaction by the oligomerization state. Nucleic Acids Res., 36, 7043-7058.
52. Asante-Appiah, E., Seeholzer, S.H. and Skalka, A.M. (1998) Structural determinants of metal-induced conformational changes in HIV-1 integrase. J. Biol. Chem., 273, 35078-35087.
53. Asante-Appiah, E. and Skalka, A.M. (1997) A metal-induced conformational change and activation of HIV-1 integrase. J. Biol. Chem., 272, 16196-16205.
54. Ramcharan, J., Colleluori, D.M., Merkel, G., Andrake, M.D. and Skalka, A.M. (2006) Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Retrovirology, 3, 34.
55. Wang, J.Y., Ling, H., Yang, W. and Craigie, R. (2001) Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein. EMBO J., 20, 7333-7343.
56. Chen, J.C., Krucinski, J., Miercke, L.J., Finer-Moore, J.S., Tang, A.H., Leavitt, A.D. and Stroud, R.M. (2000) Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc. Natl Acad. Sci. USA, 97, 8233-8238.
57. Cai, M., Zheng, R., Caffrey, M., Craigie, R., Clore, G.M. and Gronenborn, A.M. (1997) Solution structure of the N-terminal zinc binding domain of HIV-1 integrase. Nat. Struct. Biol., 4, 567-577.
58. Michel, F., Crucifix, C., Granger, F., Eiler, S., Mouscadet, J.F., Korolev, S., Agapkina, J., Ziganshin, R., Gottikh, M., Nazabal, A. et al. (2009) Structural basis for HIV-1 DNA integration in the human genome, role of the LEDGF/P75 cofactor. EMBO J., 28, 980-991.
59. Hare, S., Shun, M.C., Gupta, S.S., Valkov, E., Engelman, A. and Cherepanov, P. (2009) A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75. PLoS Pathog., 5, e1000259.
60. Zhao, Z., McKee, C.J., Kessl, J.J., Santos, W.L., Daigle, J.E., Engelman, A., Verdine, G. and Kvaratskhelia, M. (2008) Subunit-specific Protein Footprinting Reveals Significant Structural Rearrangements and a Role for N-terminal Lys-14 of HIV-1 Integrase during Viral DNA Binding. J. Biol. Chem., 283, 5632-5641.
61. Neamati, N., Lin, Z., Karki, R.G., Orr, A., Cowansage, K., Strumberg, D., Pais, G.C., Voigt, J.H., Nicklaus, M.C., Winslow, H.E. et al. (2002) Metal-dependent inhibition of HIV-1 integrase. J. Med. Chem., 45, 5661-5670.
62. Fesen, M.R., Pommier, Y., Leteurtre, F., Hiroguchi, S., Yung, J. and Kohn, K.W. (1994) Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds. Biochem. Pharmacol., 48, 595-608.
63. Molteni, V., Rhodes, D., Rubins, K., Hansen, M., Bushman, F.D. and Siegel, J.S. (2000) A new class of HIV-1 integrase inhibitors: the 3, 3, 3′, 3′-tetramethyl-1, 1′-spirobi(indan)-5, 5′, 6, 6′-tetrol family. J. Med. Chem., 43, 2031-2039.
64. Serrao, E., Odde, S., Ramkumar, K. and Neamati, N. (2009) Raltegravir, elvitegravir, and metoogravir: the birth of "me-too" HIV-1 integrase inhibitors. Retrovirology, 6, 25.
65. Kessl, J.J., Eidahl, J.O., Shkriabai, N., Zhao, Z., McKee, C.J., Hess, S., Burke, T.R. Jr and Kvaratskhelia, M. (2009) An allosteric mechanism for inhibiting HIV-1 integrase with a small molecule. Mol. Pharmacol., 76, 824-832.
66. Armon-Omer, A., Levin, A., Hayouka, Z., Butz, K., Hoppe-Seyler, F., Loya, S., Hizi, A., Friedler, A. and Loyter, A. (2008) Correlation between shiftide activity and HIV-1 integrase inhibition by a peptide selected from a combinatorial library. J. Mol. Biol., 376, 971-982.
67. Hayouka, Z., Rosenbluh, J., Levin, A., Loya, S., Lebendiker, M., Veprintsev, D., Kotler, M., Hizi, A., Loyter, A. and Friedler, A. (2007) Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium. Proc. Natl Acad. Sci. USA, 104, 8316-8321.
68. Marchand, C., Johnson, A.A., Karki, R.G., Pais, G.C., Zhang, X., Cowansage, K., Patel, T.A., Nicklaus, M.C., Burke, T.R. Jr and Pommier, Y. (2003) Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). Mol. Pharmacol., 64, 600-609.