FRET analysis reveals distinct conformations of in tetramers in the presence of viral DNA or LEDGF/p75

Nucleic Acids Research

Volumn 39, Issue 20, 2011, Pages 9009-9022

  Kessl, Jacques J ^a   Li, Min ^b   Ignatov, Michael ^a   Shkriabai, Nikolozi ^a   Eidahl, Jocelyn O ^a   Feng, Lei ^a   Musier Forsyth, Karin ^a   Craigie, Robert ^b   Kvaratskhelia, Mamuka ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTEGRASE; LENS EPITHELIUM DERIVED GROWTH FACTOR; PROTEIN P75; VIRUS DNA;

ARTICLE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; ENZYME ANALYSIS; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME STRUCTURE; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MULTIMERIZATION; PROTEIN TARGETING; RIBOSOME; STRUCTURE ANALYSIS;

DNA, VIRAL; FLUORESCENCE RESONANCE ENERGY TRANSFER; HIV INTEGRASE; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN SUBUNITS;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 80455178762     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkr581     Document Type: Article

References (70)

1. Brown, P.O. (1997) Integration. In Coffin, J.M., Hughes, S.H. and Varmus, H.E. (eds), Retroviruses. Cold Spring Harbor Laboratory, Plainview, NY, pp. 161-204.
2. Llano, M., Vanegas, M., Fregoso, O., Saenz, D., Chung, S., Peretz, M. and Poeschla, E.M. (2004) LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes. J. Virol., 78, 9524-9537.
3. Llano, M., Saenz, D.T., Meehan, A., Wongthida, P., Peretz, M., Walker, W.H., Teo, W. and Poeschla, E.M. (2006) An essential role for LEDGF/p75 in HIV integration. Science, 314, 461-464.
4. Lewinski, M.K., Yamashita, M., Emerman, M., Ciuffi, A., Marshall, H., Crawford, G., Collins, F., Shinn, P., Leipzig, J., Hannenhalli, S. et al. (2006) Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog., 2, e60.
5. Farnet, C.M. and Haseltine, W.A. (1990) Integration of human immunodeficiency virus type 1 DNA in vitro. Proc. Natl Acad. Sci. USA, 87, 4164-4168.
6. Bukrinsky, M.I., Sharova, N., McDonald, T.L., Pushkarskaya, T., Tarpley, W.G. and Stevenson, M. (1993) Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection. Proc. Natl Acad. Sci. USA, 90, 6125-6129.
7. Buckman, J.S., Bosche, W.J. and Gorelick, R.J. (2003) Human immunodeficiency virus type 1 nucleocapsid zn(2+) fingers are required for efficient reverse transcription, initial integration processes, and protection of newly synthesized viral DNA. J. Virol., 77, 1469-1480.
8. Carteau, S., Batson, S.C., Poljak, L., Mouscadet, J.F., de Rocquigny, H., Darlix, J.L., Roques, B.P., Kas, E. and Auclair, C. (1997) Human immunodeficiency virus type 1 nucleocapsid protein specifically stimulates Mg2+-dependent DNA integration in vitro. J. Virol., 71, 6225-6229.
9. Carteau, S., Gorelick, R.J. and Bushman, F.D. (1999) Coupled integration of human immunodeficiency virus type 1 cDNA ends by purified integrase in vitro: stimulation by the viral nucleocapsid protein. J. Virol., 73, 6670-6679.
10. Chen, H. and Engelman, A. (1998) The barrier-to-autointegration protein is a host factor for HIV type 1 integration. Proc. Natl Acad. Sci. USA, 95, 15270-15274.
11. Lee, M.S. and Craigie, R. (1994) Protection of retroviral DNA from autointegration: involvement of a cellular factor. Proc. Natl Acad. Sci. USA, 91, 9823-9827.
12. Lee, M.S. and Craigie, R. (1998) A previously unidentified host protein protects retroviral DNA from autointegration. Proc. Natl Acad. Sci. USA, 95, 1528-1533.
13. Cherepanov, P., Maertens, G., Proost, P., Devreese, B., Van Beeumen, J., Engelborghs, Y., De Clercq, E. and Debyser, Z. (2003) HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J. Biol. Chem, 278, 372-381.
14. Cherepanov, P., Sun, Z.Y., Rahman, S., Maertens, G., Wagner, G. and Engelman, A. (2005) Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat. Struct. Mol. Biol., 12, 526-532.
15. Shun, M.C., Raghavendra, N.K., Vandegraaff, N., Daigle, J.E., Hughes, S., Kellam, P., Cherepanov, P. and Engelman, A. (2007) LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev, 21, 1767-1778.
16. Engelman, A. (2006) Host cell factors and HIV-1 integration. Future HIV Ther, 1, 415-426.
17. 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.
18. Li, M. and Craigie, R. (2009) Nucleoprotein complex intermediates in HIV-1 integration. Methods, 47, 237-242.
19. Andrake, M.D. and Skalka, A.M. (1995) Multimerization determinants reside in both the catalytic core and C terminus of avian sarcoma virus integrase. J. Biol. Chem, 270, 29299-29306.
20. Jenkins, T.M., Engelman, A., Ghirlando, R. and Craigie, R. (1996) A soluble active mutant of HIV-1 integrase: involvement of both the core and carboxyl-terminal domains in multimerization. J. Biol. Chem., 271, 7712-7718.
21. 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.
22. 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.
23. van Gent, D.C., Elgersma, Y., Bolk, M.W., Vink, C. and Plasterk, R.H. (1991) DNA binding properties of the integrase proteins of human immunodeficiency viruses types 1 and 2. Nucleic Acids Res, 19, 3821-3827.
24. Vincent, K.A., Ellison, V., Chow, S.A. and Brown, P.O. (1993) Characterization of human immunodeficiency virus type 1 integrase expressed in Escherichia coli and analysis of variants with amino-terminal mutations. J. Virol., 67, 425-437.
25. 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.
26. 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.
27. Dyda, F., Hickman, A.B., Jenkins, T.M., Engelman, A., Craigie, R. and Davies, D.R. (1994) Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science, 266, 1981-1986.
28. Goldgur, Y., Dyda, F., Hickman, A.B., Jenkins, T.M., Craigie, R. and Davies, D.R. (1998) Three new structures of the core domain of HIV-1 integrase: an active site that binds magnesium. Proc. Natl Acad. Sci. USA, 95, 9150-9154.
29. Eijkelenboom, A.P., Lutzke, R.A., Boelens, R., Plasterk, R.H., Kaptein, R. and Hard, K. (1995) The DNA-binding domain of HIV-1 integrase has an SH3-like fold. Nat. Struct. Biol., 2, 807-810.
30. Lodi, P.J., Ernst, J.A., Kuszewski, J., Hickman, A.B., Engelman, A., Craigie, R., Clore, G.M. and Gronenborn, A.M. (1995) Solution structure of the DNA binding domain of HIV-1 integrase. Biochemistry, 34, 9826-9833.
31. Kessl, J.J., McKee, C.J., Eidahl, J.O., Shkriabai, N., Katz, A. and Kvaratskhelia, M. (2009) HIV-1 Integrase-DNA Recognition Mechanisms. Viruses, 1, 713-736.
32. Hare, S., Gupta, S.S., Valkov, E., Engelman, A. and Cherepanov, P. (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. Nature, 464, 232-236.
33. Krishnan, L., Li, X., Naraharisetty, H.L., Hare, S., Cherepanov, P. and Engelman, A. (2010) Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc. Natl Acad. Sci. USA, 107, 15910-15915.
34. De Rijck, J., Vandekerckhove, L., Gijsbers, R., Hombrouck, A., Hendrix, J., Vercammen, J., Engelborghs, Y., Christ, F. and Debyser, Z. (2006) Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication. J. Virol, 80, 11498-11509.
35. Vandekerckhove, L., Christ, F., Van Maele, B., De Rijck, J., Gijsbers, R., Van den Haute, C., Witvrouw, M. and Debyser, Z. (2006) Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. J. Virol, 80, 1886-1896.
36. Hombrouck, A., De Rijck, J., Hendrix, J., Vandekerckhove, L., Voet, A., De Maeyer, M., Witvrouw, M., Engelborghs, Y., Christ, F., Gijsbers, R. et al. (2007) Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. PLoS Pathog, 3, e47.
37. Ciuffi, A., Llano, M., Poeschla, E., Hoffmann, C., Leipzig, J., Shinn, P., Ecker, J.R. and Bushman, F. (2005) A role for LEDGF/p75 in targeting HIV DNA integration. Nat. Med, 11, 1287-1289.
38. Cherepanov, P., Devroe, E., Silver, P.A. and Engelman, A. (2004) Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase. J. Biol. Chem., 279, 48883-48892.
39. Vanegas, M., Llano, M., Delgado, S., Thompson, D., Peretz, M. and Poeschla, E. (2005) Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering. J. Cell Sci., 118(Pt 8), 1733-1743.
40. Engelman, A. and Cherepanov, P. (2008) The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog, 4, e1000046.
41. McKee, C.J., Kessl, J.J., Shkriabai, N., Dar, M.J., Engelman, A. and Kvaratskhelia, M. (2008) Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein. J. Biol. Chem., 283, 31802-31812.
42. Pandey, K.K., Sinha, S. and Grandgenett, D.P. (2007) Transcriptional coactivator LEDGF/p75 modulates human immunodeficiency virus type 1 integrase-mediated concerted integration. J. Virol., 81, 3969-3979.
43. Raghavendra, N.K. and Engelman, A. (2007) LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integration. Virology, 360, 1-5.
44. 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.
45. Cherepanov, P. (2007) LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res, 35, 113-124.
46. Maertens, G., Cherepanov, P., Pluymers, W., Busschots, K., De Clercq, E., Debyser, Z. and Engelborghs, Y. (2003) LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J. Biol. Chem, 278, 33528-33539.
47. Cherepanov, P., Surratt, D., Toelen, J., Pluymers, W., Griffith, J., De Clercq, E. and Debyser, Z. (1999) Activity of recombinant HIV-1 integrase on mini-HIV DNA. Nucleic Acids Res, 27, 2202-2210.
48. Kotova, S., Li, M., Dimitriadis, E.K. and Craigie, R. (2010) Nucleoprotein intermediates in HIV-1 DNA integration visualized by atomic force microscopy. J. Mol. Biol, 399, 491-500.
49. Zhang, X., Pais, G.C., Svarovskaia, E.S., Marchand, C., Johnson, A.A., Karki, R.G., Nicklaus, M.C., Pathak, V.K., Pommier, Y. and Burke, T.R. (2003) Azido-containing aryl beta-diketo acid HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett, 13, 1215-1219.
50. Nilsen, B.M., Haugan, I.R., Berg, K., Olsen, L., Brown, P.O. and Helland, D.E. (1996) Monoclonal antibodies against human immunodeficiency virus type 1 integrase: epitope mapping and differential effects on integrase activities in vitro. J. Virol., 70, 1580-1587.
51. Cherepanov, P., Ambrosio, A.L., Rahman, S., Ellenberger, T. and Engelman, A. (2005) Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proc. Natl Acad. Sci. USA, 102, 17308-17313.
52. Hare, S., Di Nunzio, F., Labeja, A., Wang, J., Engelman, A. and Cherepanov, P. (2009) Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog, 5, e1000515.
53. Arnold, K., Bordoli, L., Kopp, J. and Schwede, T. (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics, 22, 195-201.
54. Eswar, N., Webb, B., Marti-Renom, M.A., Madhusudhan, M.S., Eramian, D., Shen, M.Y., Pieper, U. and Sali, A. (2006) Comparative protein structure modeling using Modeller. Curr. zProtoc. Bioinformatics, Chapter 5, Unit 5 6.
55. 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.
56. Gupta, K., Diamond, T., Hwang, Y., Bushman, F. and Van Duyne, G.D. (2010) Structural properties of HIV integrase. Lens epithelium-derived growth factor oligomers. J. Biol. Chem, 285, 20303-20315.
57. Emsley, P. and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr., 60, 2126-2132.
58. Grobler, J.A., Grobler, J.A., Stillmock, K., Hu, B., Witmer, M., Felock, P., Espeseth, A.S., Wolfe, A., Egbertson, M. 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.
59. Tsiang, M., Jones, G.S., Hung, M., Samuel, D., Novikov, N., Mukund, S., Brendza, K.M., Niedziela-Majka, A., Jin, D., Liu, X. et al. (2010) Dithiothreitol causes HIV-1 integrase dimer dissociation while agents interacting with the integrase dimer interface promote dimer formation. Biochemistry, 50, 1567-1581.
60. Tsiang, M., Jones, G.S., Hung, M., Mukund, S., Han, B., Liu, X., Babaoglu, K., Lansdon, E., Chen, X., Todd, J. et al. (2009) Affinities between the binding partners of the HIV-1 integrase dimer-lens epithelium-derived growth factor (IN dimer-LEDGF) complex. J. Biol. Chem., 284, 33580-33599.
61. Botbol, Y., Raghavendra, N.K., Rahman, S., Engelman, A. and Lavigne, M. (2008) Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro. Nucleic Acids Res., 36, 1237-1246.
62. 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.
63. 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.
64. Zhu, K., Dobard, C. and Chow, S.A. (2004) Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J. Virol., 78, 5045-5055.
65. Kessl, J.J., Eidahl, J.O., Shkriabai, N., Zhao, Z., McKee, C.J., Hess, S., Burke, T.R. Jr, Kvaratskhelia, M. et al. (2009) An allosteric mechanism for inhibiting HIV-1 integrase with a small molecule. Mol. Pharmacol., 76, 824-832.
66. Huang, F., Lerner, E., Sato, S., Amir, D., Haas, E. and Fersht, A. (2009) Time-resolved FRET study shows a compact denatured state of the B domain of Protein A. Biochemistry, 48, 3468-3476.
67. Llano, M., Delgado, S., Vanegas, M. and Poeschla, E.M. (2004) Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase. J. Biol. Chem., 279, 55570-55577.
68. Christ, F., Voet, A., Marchand, A., Nicolet, S., Desimmie, B.A., Marchand, D., Bardiot, D., Van der Veken, N.J., Van Remoortel, B., Strelkov, S.V. et al. (2010) Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat. Chem. Biol., 6, 442-448.
69. Molteni, V., Greenwald, J., Rhodes, D., Hwang, Y., Kwiatkowski, W., Bushman, F.D., Siegel, J.S. and Choe, S. (2001) Identification of a small-molecule binding site at the dimer interface of the HIV integrase catalytic domain. Acta Crystallogr. D Biol. Crystallogr., 57(Pt 4), 536-544.
70. Al-Mawsawi, L.Q., Fikkert, V., Dayam, R., Witvrouw, M., Burke, T.R. Jr, Borchers, C.H. and Neamati, N. (2006) Discovery of a small-molecule HIV-1 integrase inhibitor-binding site. Proc. Natl Acad. Sci. USA, 103, 10080-10085.