Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function

Nature

Volumn 530, Issue 7590, 2016, Pages 358-361

  Ballandras Colas, Allison ^a   Brown, Monica ^b   Cook, Nicola J ^c   Dewdney, Tamaria G ^a   Demeler, Borries ^d   Cherepanov, Peter ^c,e   Lyumkis, Dmitry ^b   Engelman, Alan N ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^c THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^d UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^e IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

INTASOME; INTEGRASE; PROTEOME; TETRAMER; UNCLASSIFIED DRUG; VIRUS DNA;

CATALYSIS; DNA; ENZYME; ENZYME ACTIVITY; LIFE CYCLE; RODENT; TUMOR; VIRUS;

ARTICLE; BETARETROVIRUS; CARBOXY TERMINAL SEQUENCE; CATALYSIS; CRYOELECTRON MICROSCOPY; DNA FLANKING REGION; DNA INTEGRATION; DNA RECOMBINATION; MOUSE; MOUSE MAMMARY TUMOR VIRUS; NONHUMAN; PRIORITY JOURNAL; SPUMAVIRUS; X RAY CRYSTALLOGRAPHY; CHEMISTRY; ENZYME ACTIVE SITE; ENZYMOLOGY; GENETICS; METABOLISM; MOLECULAR MODEL; PROTEIN MULTIMERIZATION; PROTEIN QUATERNARY STRUCTURE; ULTRASTRUCTURE; VIRUS DNA CELL DNA INTERACTION;

BETARETROVIRUS; HUMAN SPUMARETROVIRUS; SPUMAVIRUS;

CATALYTIC DOMAIN; CRYOELECTRON MICROSCOPY; CRYSTALLOGRAPHY, X-RAY; DNA, VIRAL; INTEGRASES; MAMMARY TUMOR VIRUS, MOUSE; MODELS, MOLECULAR; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, QUATERNARY; SPUMAVIRUS; VIRUS INTEGRATION;

EID: 84959017190     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature16955     Document Type: Article

References (61)

1. Craigie, R., Bushman, F. D. HIV DNA integration. Cold Spring Harb. Perspect. Med. 2, a006890 (2012).
2. Hare, S., Gupta, S. S., Valkov, E., Engelman, A., Cherepanov, P. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464, 232-236 (2010).
3. Maertens, G. N., Hare, S., Cherepanov, P. The mechanism of retroviral integration from X-ray structures of its key intermediates. Nature 468, 326-329 (2010).
4. Hare, S., Maertens, G. N., Cherepanov, P. 3-Processing and strand transfer catalysed by retroviral integrase in crystallo. EMBO J. 31, 3020-3028 (2012).
5. Maskell, D. P. et al. Structural basis for retroviral integration into nucleosomes. Nature 523, 366-369 (2015).
6. Yang, Z. N., Mueser, T. C., Bushman, F. D., Hyde, C. C. Crystal structure of an active two-domain derivative of Rous sarcoma virus integrase. J. Mol. Biol. 296, 535-548 (2000).
7. Wang, J. Y., Ling, H., Yang, W., Craigie, R. Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein. EMBO J. 20, 7333-7343 (2001).
8. Bao, K. K. et al. Functional oligomeric state of avian sarcoma virus integrase. J. Biol. Chem. 278, 1323-1327 (2003).
9. Li, M., Mizuuchi, M., Burke, T. R., Jr & Craigie, R. Retroviral DNA integration: reaction pathway and critical intermediates. EMBO J. 25, 1295-1304 (2006).
10. Hare, S. et al. 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 (2009).
11. Majors, J. E., Varmus, H. E. Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus. Nature 289, 253-258 (1981).
12. Roth, M. J., Schwartzberg, P. L., Goff, S. P. Structure of the termini of DNA intermediates in the integration of retroviral DNA: dependence on IN function and terminal DNA sequence. Cell 58, 47-54 (1989).
13. Craigie, R., Fujiwara, T., Bushman, F. The IN protein of Moloney murine leukemia virus processes the viral DNA ends and accomplishes their integration in vitro. Cell 62, 829-837 (1990).
14. Ellison, V., Brown, P. O. A stable complex between integrase and viral DNA ends mediates human immunodeficiency virus integration in vitro. Proc. Natl Acad. Sci. USA 91, 7316-7320 (1994).
15. DiMaio, F. et al. Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density guided iterative local refinement. Nature Methods 12, 361-365 (2015).
16. Kudryashev, M. et al. Structure of the type VI secretion system contractile sheath. Cell 160, 952-962 (2015).
17. Wang, R. Y. et al. De novo protein structure determination from near atomicresolution cryo-EM maps. Nature Methods 12, 335-338 (2015).
18. van Gent, D. C., Vink, C., Groeneger, A. A., Plasterk, R. H. Complementation between HIV integrase proteins mutated in different domains. EMBO J. 12, 3261-3267 (1993).
19. Engelman, A., Bushman, F. D., Craigie, R. Identification of discrete functional domains of HIV-1 integrase and their organization within an active multimeric complex. EMBO J. 12, 3269-3275 (1993).
20. Yang, F., Roth, M. J. Assembly and catalysis of concerted two-end integration events by Moloney murine leukemia virus integrase. J. Virol. 75, 9561-9570 (2001).
21. Diamond, T. L., Bushman, F. D. Division of labor within human immunodeficiency virus integrase complexes: determinants of catalysis and target DNA capture. J. Virol. 79, 15376-15387 (2005).
22. Baker, T. A., Mizuuchi, M., Savilahti, H., Mizuuchi, K. Division of labor among monomers within the Mu transposase tetramer. Cell 74, 723-733 (1993).
23. Jenkins, T. M., Esposito, D., Engelman, A., Craigie, R. Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking. EMBO J. 16, 6849-6859 (1997).
24. Yin, Z., Shi, K., Banerjee, S., Grandgenett, D. P., Aihara, H. Crystal structure of the Rous sarcoma virus intasome. Nature http://dx.doi.org/10.1038/nature16950 (this issue).
25. Faure, A. et al. HIV-1 integrase crosslinked oligomers are active in vitro. Nucleic Acids Res. 33, 977-986 (2005).
26. Bera, S., Pandey, K. K., Vora, A. C., Grandgenett, D. P. Molecular interactions between HIV-1 integrase and the two viral DNA ends within the synaptic complex that mediates concerted integration. J. Mol. Biol. 389, 183-198 (2009).
27. Lee, S. P., Xiao, J., Knutson, J. R., Lewis, M. S., Han, M. K. Zn2+ promotes the self-association of human immunodeficiency virus type-1 integrase in vitro. Biochemistry 36, 173-180 (1997).
28. Heuer, T. S., Brown, P. O. Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase-DNA complex. Biochemistry 37, 6667-6678 (1998).
29. Serrao, E., Ballandras-Colas, A., Cherepanov, P., Maertens, G. N., Engelman, A. N. Key determinants of target DNA recognition by retroviral intasomes. Retrovirology 12, 39 (2015).
30. Engelman, A., Craigie, R. Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. J. Virol. 66, 6361-6369 (1992).
31. Ballandras-Colas, A., Naraharisetty, H., Li, X., Serrao, E., Engelman, A. Biochemical characterization of novel retroviral integrase proteins. PLoS ONE 8, e76638 (2013).
32. Cherepanov, P. LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res. 35, 113-124 (2007).
33. Demeler, B. et al. UltraScan-III version 2.2: a comprehensive data analysis software package for analytical ultracentrifugation experiments http://www. ultrascan3.uthscsa.edu/(2014).
34. Laue, T. M., Shah, B. D., Ridgeway, T. M., Pelletier, S. L. in Analytical Ultracentrifugation in Biochemistry and Polymer Science (eds Harding, S. E., Rowe, A. J., Horton, J. C.) 90-125 (Royal Society of Chemistry, 1992).
35. Demeler, B. in Current Protocols in Protein Science (eds Coligan, J. E. et al.) Ch. 7, Unit 7.13, 7.13.1-7.13.24 (Wiley, 2010).
36. Brookes, E., Cao, W., Demeler, B. A two-dimensional spectrum analysis for sedimentation velocity experiments of mixtures with heterogeneity in molecular weight and shape. Eur. Biophys. J. 39, 405-414 (2010).
37. Schuck, P., Demeler, B. Direct sedimentation analysis of interference optical data in analytical ultracentrifugation. Biophys. J. 76, 2288-2296 (1999).
38. Brookes, E. H., Demeler, B. in Proceedings of the 9th Annual Conference on Genetic and Evolutionary Computation 361-368 (Association for Computing Machinery, 2007).
39. Demeler, B., Brookes, E. Monte Carlo analysis of sedimentation experiments. Colloid Polym. Sci. 286, 129-137 (2008).
40. Kabsch, W. XDS. Acta Crystallogr. D 66, 125-132 (2010).
41. Evans, P. R., Murshudov, G. N. How good are my data and what is the resolution Acta Crystallogr. D 69, 1204-1214 (2013).
42. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
43. Bujacz, G. et al. High-resolution structure of the catalytic domain of avian sarcoma virus integrase. J. Mol. Biol. 253, 333-346 (1995).
44. Chen, J. C.-H. et al. 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 (2000).
45. Morris, R. J., Perrakis, A., Lamzin, V. S. ARP/wARP and automatic interpretation of protein electron density maps. Methods Enzymol. 374, 229-244 (2003).
46. Emsley, P., Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126-2132 (2004).
47. Adams, P. D. et al. The Phenix software for automated determination of macromolecular structures. Methods 55, 94-106 (2011).
48. Murshudov, G. N., Vagin, A. A., Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240-255 (1997).
49. Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12-21 (2010).
50. Suloway, C. et al. Automated molecular microscopy: the new Leginon system. J. Struct. Biol. 151, 41-60 (2005).
51. Li, X. et al. Electron counting and beam-induced motion correction enable nearatomic-resolution single-particle cryo-EM. Nature Methods 10, 584-590 (2013).
52. Lyumkis, D. et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342, 1484-1490 (2013).
53. Grant, T., Grigorieff, N. Measuring the optimal exposure for single particle cryo-EM using a 2.6 Å reconstruction of rotavirus VP6. eLife 4, e06980 (2015).
54. Lander, G. C. et al. Appion: an integrated, database-driven pipeline to facilitate EM image processing. J. Struct. Biol. 166, 95-102 (2009).
55. Sorzano, C. O. et al. A clustering approach to multireference alignment of singleparticle projections in electron microscopy. J. Struct. Biol. 171, 197-206 (2010).
56. Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519-530 (2012).
57. Lyumkis, D., Vinterbo, S., Potter, C. S., Carragher, B. Optimod-an automated approach for constructing and optimizing initial models for single-particle electron microscopy. J. Struct. Biol. 184, 417-426 (2013).
58. Grigorieff, N. FREALIGN: high-resolution refinement of single particle structures. J. Struct. Biol. 157, 117-125 (2007).
59. Lyumkis, D., Brilot, A. F., Theobald, D. L., Grigorieff, N. Likelihood-based classification of cryo-EM images using FREALIGN. J. Struct. Biol. 183, 377-388 (2013).
60. DiMaio, F., Zhang, J., Chiu, W., Baker, D. Cryo-EM model validation using independent map reconstructions. Protein Sci. 22, 865-868 (2013).
61. Robert, X., Gouet, P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42, W320-W324 (2014).