Crystal structure of the Rous sarcoma virus intasome

Yin, Zhiqi; Shi, Ke; Banerjee, Surajit; Pandey, Krishan K.; Bera, Sibes; Grandgenett, Duane P.; Aihara, Hideki

doi:10.1038/nature16950

Title: Crystal structure of the Rous sarcoma virus intasome

Journal Article · Wed Feb 17 00:00:00 EST 2016 · Nature (London)

DOI:https://doi.org/10.1038/nature16950· OSTI ID:1239418

Yin, Zhiqi ^[1]; Shi, Ke ^[1]; Banerjee, Surajit ^[2]; Pandey, Krishan K. ^[3]; Bera, Sibes ^[3]; Grandgenett, Duane P. ^[3]; Aihara, Hideki ^[1]

Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Biochemistry, Molecular Biology and Biophysics. Inst. for Molecular Virology. Masonic Cancer Center
Cornell Univ., Lemont, IL (United States). Advanced Photon Source. Northeastern Collaborative Access Team
Saint Louis Univ., St. Louis, MO (United States). Health Sciences Center. Inst. for Molecular Virology

Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction. Although structures of the tetrameric integrase–DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers, the architecture of a canonical three-domain integrase bound to DNA remained elusive. In this paper, we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein–DNA and protein–protein contacts that show both conserved and distinct features compared with those observed for prototype foamy virus integrase. Finally, our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Univ. of Minnesota, Minneapolis, MN (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)

Contributing Organization:: Cornell Univ., Lemont, IL (United States). Advanced Photon Source; Saint Louis Univ., St. Louis, MO (United States)

Grant/Contract Number:: AC02-06CH11357; P41 GM103403; GM109770; AI087098; AI100682

OSTI ID:: 1239418

Journal Information:: Nature (London), Vol. 530, Issue 7590; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 64 works

Citation information provided by
Web of Science

References (45)

Linking Crystallographic Model and Data Quality Karplus, P. A.; Diederichs, K. Science, Vol. 336, Issue 6084 https://doi.org/10.1126/science.1218231	journal	May 2012
Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein Wang, J. -Y. The EMBO Journal, Vol. 20, Issue 24 https://doi.org/10.1093/emboj/20.24.7333	journal	December 2001
Construction and analysis of deletion mutations in the pol gene of moloney murine leukemia virus: A new viral function required for productive infection Schwartzberg, Pamela; Colicelli, John; Goff, Stephen P. Cell, Vol. 37, Issue 3 https://doi.org/10.1016/0092-8674(84)90439-2	journal	July 1984
Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function Ballandras-Colas, Allison; Brown, Monica; Cook, Nicola J. Nature, Vol. 530, Issue 7590 https://doi.org/10.1038/nature16955	journal	February 2016
Crystal structure of an active two-domain derivative of rous sarcoma virus integrase 1 1Edited by I. A. Wilson Yang, Zhong-Ning; Mueser, Timothy C.; Bushman, Frederic D. Journal of Molecular Biology, Vol. 296, Issue 2 https://doi.org/10.1006/jmbi.1999.3463	journal	February 2000
Retroviral intasome assembly and inhibition of DNA strand transfer Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene Nature, Vol. 464, Issue 7286 https://doi.org/10.1038/nature08784	journal	January 2010
Assembly of prototype foamy virus strand transfer complexes on product DNA bypassing catalysis of integration: Assembly of PFV Strand Transfer Complexes on Product DNA Yin, Zhiqi; Lapkouski, Mikalai; Yang, Wei Protein Science, Vol. 21, Issue 12 https://doi.org/10.1002/pro.2166	journal	October 2012
The mechanism of retroviral integration from X-ray structures of its key intermediates Maertens, Goedele N.; Hare, Stephen; Cherepanov, Peter Nature, Vol. 468, Issue 7321 https://doi.org/10.1038/nature09517	journal	November 2010
Structural and sequencing analysis of local target DNA recognition by MLV integrase Aiyer, S.; Rossi, P.; Malani, N. Nucleic Acids Research, Vol. 43, Issue 11 https://doi.org/10.1093/nar/gkv410	journal	May 2015
Key determinants of target DNA recognition by retroviral intasomes Serrao, Erik; Ballandras-Colas, Allison; Cherepanov, Peter Retrovirology, Vol. 12, Issue 1 https://doi.org/10.1186/s12977-015-0167-3	journal	April 2015
Crystal structure of the nucleosome core particle at 2.8 Å resolution Luger, Karolin; Mäder, Armin W.; Richmond, Robin K. Nature, Vol. 389, Issue 6648 https://doi.org/10.1038/38444	journal	September 1997
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
HIV DNA Integration Craigie, R.; Bushman, F. D. Cold Spring Harbor Perspectives in Medicine, Vol. 2, Issue 7 https://doi.org/10.1101/cshperspect.a006890	journal	May 2012
Characterization of the R263K Mutation in HIV-1 Integrase That Confers Low-Level Resistance to the Second-Generation Integrase Strand Transfer Inhibitor Dolutegravir Quashie, P. K.; Mesplede, T.; Han, Y. -S. Journal of Virology, Vol. 86, Issue 5 https://doi.org/10.1128/JVI.06591-11	journal	December 2011
Comparative Protein Modelling by Satisfaction of Spatial Restraints Šali, Andrej; Blundell, Tom L. Journal of Molecular Biology, Vol. 234, Issue 3 https://doi.org/10.1006/jmbi.1993.1626	journal	December 1993
A Possible Role for the Asymmetric C-Terminal Domain Dimer of Rous Sarcoma Virus Integrase in Viral DNA Binding Shi, Ke; Pandey, Krishan K.; Bera, Sibes PLoS ONE, Vol. 8, Issue 2 https://doi.org/10.1371/journal.pone.0056892	journal	February 2013
The Mu transpososome structure sheds light on DDE recombinase evolution Montaño, Sherwin P.; Pigli, Ying Z.; Rice, Phoebe A. Nature, Vol. 491, Issue 7424 https://doi.org/10.1038/nature11602	journal	November 2012
The participation of DNA in Rofs sarcoma virus production Temin, Howard M. Virology, Vol. 23, Issue 4 https://doi.org/10.1016/0042-6822(64)90232-6	journal	August 1964
Avian Retrovirus U3 and U5 DNA Inverted Repeats: ROLE OF NONSYMMETRICAL NUCLEOTIDES IN PROMOTING FULL-SITE INTEGRATION BY PURIFIED VIRION AND BACTERIAL RECOMBINANT INTEGRASES Vora, Ajaykumar C.; Chiu, Roger; McCord, Mark Journal of Biological Chemistry, Vol. 272, Issue 38 https://doi.org/10.1074/jbc.272.38.23938	journal	September 1997
Multiple Integrase Functions Are Required to Form the Native Structure of the Human Immunodeficiency Virus Type I Intasome Chen, Hongmin; Wei, Shui-Qing; Engelman, Alan Journal of Biological Chemistry, Vol. 274, Issue 24 https://doi.org/10.1074/jbc.274.24.17358	journal	June 1999
Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA Gupta, Kushol; Curtis, Joseph E.; Krueger, Susan Structure, Vol. 20, Issue 11 https://doi.org/10.1016/j.str.2012.08.023	journal	November 2012
Deciphering key features in protein structures with the new ENDscript server Robert, Xavier; Gouet, Patrice Nucleic Acids Research, Vol. 42, Issue W1 https://doi.org/10.1093/nar/gku316	journal	April 2014
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
The retrovirus pol gene encodes a product required for DNA integration: identification of a retrovirus int locus. Panganiban, A. T.; Temin, H. M. Proceedings of the National Academy of Sciences, Vol. 81, Issue 24 https://doi.org/10.1073/pnas.81.24.7885	journal	December 1984
Atomic Resolution Structures of the Core Domain of Avian Sarcoma Virus Integrase and Its D64N Mutant ^† ^, ^‡ Lubkowski, Jacek; Dauter, Zbigniew; Yang, Fan Biochemistry, Vol. 38, Issue 41 https://doi.org/10.1021/bi991362q	journal	October 1999
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
A mutant murine leukemia virus with a single missense codon in pol is defective in a function affecting integration. Donehower, L. A.; Varmus, H. E. Proceedings of the National Academy of Sciences, Vol. 81, Issue 20 https://doi.org/10.1073/pnas.81.20.6461	journal	October 1984
Structural basis for retroviral integration into nucleosomes Maskell, Daniel P.; Renault, Ludovic; Serrao, Erik Nature, Vol. 523, Issue 7560 https://doi.org/10.1038/nature14495	journal	June 2015
Human immunodeficiency virus type 1 integrase: arrangement of protein domains in active cDNA complexes Gao, K. The EMBO Journal, Vol. 20, Issue 13 https://doi.org/10.1093/emboj/20.13.3565	journal	July 2001
MOLREP an Automated Program for Molecular Replacement Vagin, A.; Teplyakov, A. Journal of Applied Crystallography, Vol. 30, Issue 6, p. 1022-1025 https://doi.org/10.1107/S0021889897006766	journal	December 1997
A 32,000-Dalton nucleic acid-binding protein from avian retravirus cores possesses DNA endonuclease activity Grandgenett, Duane P.; Vora, Ajaykumar C.; Schiff, Ron D. Virology, Vol. 89, Issue 1 https://doi.org/10.1016/0042-6822(78)90046-6	journal	August 1978
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Localization of ASV Integrase-DNA Contacts by Site-Directed Crosslinking and their Structural Analysis Peletskaya, Elena; Andrake, Mark; Gustchina, Alla PLoS ONE, Vol. 6, Issue 12 https://doi.org/10.1371/journal.pone.0027751	journal	December 2011
Structure-Based Mutational Analysis of the C-Terminal DNA-Binding Domain of Human Immunodeficiency Virus Type 1 Integrase: Critical Residues for Protein Oligomerization and DNA Binding Lutzke, Ramon A. Puras; Plasterk, Ronald H. A. Journal of Virology, Vol. 72, Issue 6 https://doi.org/10.1128/JVI.72.6.4841-4848.1998	journal	June 1998
Programmable RNA targeting by bacterial Argonaute nucleases with unconventional guide binding and cleavage specificity Lisitskaya, Lidiya; Shin, Yeonoh; Agapov, Aleksei Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-32079-5	journal	August 2022
Host ANP32A mediates the assembly of the influenza virus replicase Carrique, Loïc; Fan, Haitian; Walker, Alexander P. Nature, Vol. 587, Issue 7835 https://doi.org/10.1038/s41586-020-2927-z	journal	November 2020
Architecture of a Full-length Retroviral Integrase Monomer and Dimer, Revealed by Small Angle X-ray Scattering and Chemical Cross-linking Bojja, Ravi S.; Andrake, Mark D.; Weigand, Steven Journal of Biological Chemistry, Vol. 286, Issue 19 https://doi.org/10.1074/jbc.m110.212571	journal	March 2011
Rous Sarcoma Virus Synaptic Complex Capable of Concerted Integration Is Kinetically Trapped by Human Immunodeficiency Virus Integrase Strand Transfer Inhibitors Pandey, Krishan K.; Bera, Sibes; Korolev, Sergey Journal of Biological Chemistry, Vol. 289, Issue 28 https://doi.org/10.1074/jbc.m114.573311	journal	May 2014
Structural Organization of Avian Retrovirus Integrase in Assembled Intasomes Mediating Full-site Integration Vora, Ajaykumar; Bera, Sibes; Grandgenett, Duane Journal of Biological Chemistry, Vol. 279, Issue 18 https://doi.org/10.1074/jbc.m314270200	journal	February 2004
Processing of Viral DNA Ends Channels the HIV-1 Integration Reaction to Concerted Integration Li, Min; Craigie, Robert Journal of Biological Chemistry, Vol. 280, Issue 32 https://doi.org/10.1074/jbc.m505367200	journal	June 2005
Molecular and Genetic Determinants of Rous Sarcoma Virus Integrase for Concerted DNA Integration Chiu, Roger; Grandgenett, Duane P. Journal of Virology, Vol. 77, Issue 11 https://doi.org/10.1128/jvi.77.11.6482-6492.2003	journal	June 2003
An Amino Acid in the Central Catalytic Domain of Three Retroviral Integrases That Affects Target Site Selection in Nonviral DNA Harper, Amy L.; Sudol, Malgorzata; Katzman, Michael Journal of Virology, Vol. 77, Issue 6 https://doi.org/10.1128/jvi.77.6.3838-3845.2003	journal	March 2003
Weak Palindromic Consensus Sequences Are a Common Feature Found at the Integration Target Sites of Many Retroviruses Wu, Xiaolin; Li, Yuan; Crise, Bruce Journal of Virology, Vol. 79, Issue 8 https://doi.org/10.1128/jvi.79.8.5211-5214.2005	journal	April 2005
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010

Cited By (29)

Retroviruses integrate into a shared, non-palindromic DNA motif Kirk, Paul D. W.; Huvet, Maxime; Melamed, Anat Nature Microbiology, Vol. 2, Issue 2 https://doi.org/10.1038/nmicrobiol.2016.212	journal	November 2016
Integration site selection by retroviruses and transposable elements in eukaryotes Sultana, Tania; Zamborlini, Alessia; Cristofari, Gael Nature Reviews Genetics, Vol. 18, Issue 5 https://doi.org/10.1038/nrg.2017.7	journal	March 2017
Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer Wilson, Marcus D.; Renault, Ludovic; Maskell, Daniel P. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12007-w	journal	September 2019
The free energy landscape of retroviral integration Vanderlinden, Willem; Brouns, Tine; Walker, Philipp U. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12649-w	journal	October 2019
Structures of a RAG-like transposase during cut-and-paste transposition Liu, Chang; Yang, Yang; Schatz, David G. Nature, Vol. 575, Issue 7783 https://doi.org/10.1038/s41586-019-1753-7	journal	November 2019
Structure of a P element transposase–DNA complex reveals unusual DNA structures and GTP-DNA contacts Ghanim, George E.; Kellogg, Elizabeth H.; Nogales, Eva Nature Structural & Molecular Biology, Vol. 26, Issue 11 https://doi.org/10.1038/s41594-019-0319-6	journal	October 2019
How mouse RAG recombinase avoids DNA transposition Chen, Xuemin; Cui, Yanxiang; Wang, Huaibin Nature Structural & Molecular Biology, Vol. 27, Issue 2 https://doi.org/10.1038/s41594-019-0366-z	journal	February 2020
Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition Engelman, Alan N. Journal of Biological Chemistry, Vol. 294, Issue 41 https://doi.org/10.1074/jbc.rev119.006901	journal	August 2019
The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study Balasubramanian, Sangeetha; Rajagopalan, Muthukumaran; Bojja, Ravi Shankar Journal of Biomolecular Structure and Dynamics, Vol. 35, Issue 16 https://doi.org/10.1080/07391102.2016.1257955	journal	November 2016
Multimerization of HIV-1 integrase hinges on conserved SH3-docking platforms Galilee, Meytal; Alian, Akram BioRxiv https://doi.org/10.1101/301721	posted_content	April 2018
Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome Passos, Dario Oliveira; Li, Min; Yang, Renbin Science, Vol. 355, Issue 6320 https://doi.org/10.1126/science.aah5163	journal	January 2017
Structural basis for strand-transfer inhibitor binding to HIV intasomes Passos, Dario Oliveira; Li, Min; Jóźwik, Ilona K. Science, Vol. 367, Issue 6479 https://doi.org/10.1126/science.aay8015	journal	January 2020
Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration Matysiak, Julien; Lesbats, Paul; Mauro, Eric Retrovirology, Vol. 14, Issue 1 https://doi.org/10.1186/s12977-017-0363-4	journal	July 2017
Recent advances in retroviruses via cryo-electron microscopy Mak, Johnson; de Marco, Alex Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0405-6	journal	February 2018
Retrotransposon targeting to RNA polymerase III-transcribed genes Cheung, Stephanie; Manhas, Savrina; Measday, Vivien Mobile DNA, Vol. 9, Issue 1 https://doi.org/10.1186/s13100-018-0119-2	journal	April 2018
Structural Implications of Genotypic Variations in HIV-1 Integrase From Diverse Subtypes Rogers, Leonard; Obasa, Adetayo E.; Jacobs, Graeme B. Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.01754	journal	August 2018
Structural Insights on Retroviral DNA Integration: Learning from Foamy Viruses Lee, Ga-Eun; Mauro, Eric; Parissi, Vincent Viruses, Vol. 11, Issue 9 https://doi.org/10.3390/v11090770	journal	August 2019
Retroviruses integrate into a shared, non-palindromic DNA motif. Kirk, Paul; Huvet, Maxime; Melamed, Anat Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.25498	text	January 2016
Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer. Wilson, Marcus D.; Renault, Ludovic; Maskell, Daniel P. The Francis Crick Institute https://doi.org/10.25418/crick.11619861	text	January 2020
The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study Balasubramanian, Sangeetha; Rajagopalan, Muthukumaran; Bojja, Ravi Shankar Taylor & Francis https://doi.org/10.6084/m9.figshare.4263725.v1	text	January 2016
Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer. Wilson, Marcus D.; Renault, Ludovic; Maskell, Daniel P. The Francis Crick Institute https://doi.org/10.25418/crick.11619861.v1	text	January 2020
The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study Balasubramanian, Sangeetha; Rajagopalan, Muthukumaran; Bojja, Ravi Shankar Taylor & Francis https://doi.org/10.6084/m9.figshare.4263725	text	January 2016
Prototype foamy virus integrase is promiscuous for target choice Mackler, R. M.; Lopez, M. A.; Osterhage, M. J. Biochemical and Biophysical Research Communications, Vol. 503, Issue 3 https://doi.org/10.1016/j.bbrc.2018.07.031	journal	September 2018
Retroviral DNA Integration Lesbats, Paul; Engelman, Alan N.; Cherepanov, Peter Chemical Reviews, Vol. 116, Issue 20 https://doi.org/10.1021/acs.chemrev.6b00125	journal	May 2016
Differential assembly of Rous sarcoma virus tetrameric and octameric intasomes is regulated by the C-terminal domain and tail region of integrase Bera, Sibes; Pandey, Krishan K.; Aihara, Hideki Journal of Biological Chemistry, Vol. 293, Issue 42 https://doi.org/10.1074/jbc.ra118.004768	journal	October 2018
DNA minicircles clarify the specific role of DNA structure on retroviral integration Pasi, Marco; Mornico, Damien; Volant, Stevenn Nucleic Acids Research, Vol. 44, Issue 16 https://doi.org/10.1093/nar/gkw651	journal	July 2016
A supramolecular assembly mediates lentiviral DNA integration Ballandras-Colas, Allison; Maskell, Daniel P.; Serrao, Erik Science, Vol. 355, Issue 6320 https://doi.org/10.1126/science.aah7002	journal	January 2017
Dissecting Virus Infectious Cycles by Cryo-Electron Microscopy Lee, Kelly K.; Gui, Long PLOS Pathogens, Vol. 12, Issue 6 https://doi.org/10.1371/journal.ppat.1005625	journal	June 2016
Target DNA bending by the Mu transpososome promotes careful transposition and prevents its reversal Fuller, James R.; Rice, Phoebe A. eLife, Vol. 6 https://doi.org/10.7554/elife.21777	journal	February 2017