Crystal structure of the V(D)J recombinase RAG1–RAG2

Kim, Min-Sung; Lapkouski, Mikalai; Yang, Wei; Gellert, Martin

doi:10.1038/nature14174

Title: Crystal structure of the V(D)J recombinase RAG1–RAG2

Journal Article · Wed Feb 18 00:00:00 EST 2015 · Nature (London)

DOI:https://doi.org/10.1038/nature14174· OSTI ID:1247328

Kim, Min-Sung ^[1]; Lapkouski, Mikalai ^[2]; Yang, Wei ^[1]; Gellert, Martin ^[1]

National Inst. of Health (NIH), Bethesda, MD (United States)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); National Inst. of Health (NIH), Bethesda, MD (United States)

V(D)J recombination in the vertebrate immune system generates a highly diverse population of immunoglobulins and T-cell receptors by combinatorial joining of segments of coding DNA. The RAG1–RAG2 protein complex initiates this site-specific recombination by cutting DNA at specific sites flanking the coding segments. Here we report the crystal structure of the mouse RAG1–RAG2 complex at 3.2 Å resolution. The 230-kilodalton RAG1–RAG2 heterotetramer is ‘Y-shaped’, with the amino-terminal domains of the two RAG1 chains forming an intertwined stalk. Each RAG1–RAG2 heterodimer composes one arm of the ‘Y’, with the active site in the middle and RAG2 at its tip. The RAG1–RAG2 structure rationalizes more than 60 mutations identified in immunodeficient patients, as well as a large body of genetic and biochemical data. Here, the architectural similarity between RAG1 and the hairpin-forming transposases Hermes and Tn5 suggests the evolutionary conservation of these DNA rearrangements.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of Health

OSTI ID:: 1247328

Journal Information:: Nature (London), Vol. 518, Issue 7540; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 120 works

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References (63)

Sequences at the somatic recombination sites of immunoglobulin light-chain genes Sakano, Hitoshi; Hüppi, Konrad; Heinrich, Günther Nature, Vol. 280, Issue 5720 https://doi.org/10.1038/280288a0	journal	July 1979
The Mechanism of V(D)J Joining: Lessons from Molecular, Immunological, and Comparative Analyses Lewis, Susanna M. Advances in Immunology https://doi.org/10.1016/S0065-2776(08)60450-2	book	January 1994
V(D)J Recombination: RAG Proteins, Repair Factors, and Regulation Gellert, Martin Annual Review of Biochemistry, Vol. 71, Issue 1 https://doi.org/10.1146/annurev.biochem.71.090501.150203	journal	June 2002
V(D)J Recombination: Mechanisms of Initiation Schatz, David G.; Swanson, Patrick C. Annual Review of Genetics, Vol. 45, Issue 1 https://doi.org/10.1146/annurev-genet-110410-132552	journal	December 2011
Modernizing the Nonhomologous End-Joining Repertoire: Alternative and Classical NHEJ Share the Stage Deriano, Ludovic; Roth, David B. Annual Review of Genetics, Vol. 47, Issue 1 https://doi.org/10.1146/annurev-genet-110711-155540	journal	November 2013
RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination Oettinger, M.; Schatz, D.; Gorka, C. Science, Vol. 248, Issue 4962 https://doi.org/10.1126/science.2360047	journal	June 1990
The V(D)J recombination activating gene, RAG-1 Schatz, David G.; Oettinger, Marjorie A.; Baltimore, David Cell, Vol. 59, Issue 6 https://doi.org/10.1016/0092-8674(89)90760-5	journal	December 1989
Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps McBlane, J. Fraser; van Gent, Dik C.; Ramsden, Dale A. Cell, Vol. 83, Issue 3 https://doi.org/10.1016/0092-8674(95)90116-7	journal	November 1995
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system Agrawal, Alka; Eastman, Quinn M.; Schatz, David G. Nature, Vol. 394, Issue 6695 https://doi.org/10.1038/29457	journal	August 1998
DNA Transposition by the RAG1 and RAG2 Proteins Hiom, Kevin; Melek, Meni; Gellert, Martin Cell, Vol. 94, Issue 4 https://doi.org/10.1016/S0092-8674(00)81587-1	journal	August 1998
A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry Journal of Allergy and Clinical Immunology, Vol. 133, Issue 4 https://doi.org/10.1016/j.jaci.2013.10.007	journal	April 2014
Immunodeficiency mutation databases (IDbases) Piirilä, Hilkka; Väliaho, Jouni; Vihinen, Mauno Human Mutation, Vol. 27, Issue 12 https://doi.org/10.1002/humu.20405	journal	December 2006
Analysis of regions of RAG-2 important for V(D)J recombination Cuomo, Christina A.; Oettinger, Marjorie A. Nucleic Acids Research, Vol. 22, Issue 10 https://doi.org/10.1093/nar/22.10.1810	journal	January 1994
Definition of a core region of RAG-2 that is functional in V(D)J recombination Sadofsky, Moshe J.; Hesse, Joanne E.; Gellert, Martin Nucleic Acids Research, Vol. 22, Issue 10 https://doi.org/10.1093/nar/22.10.1805	journal	January 1994
Expression and V(D)J recombination activity of mutated RAG-1 proteins Sadofsky, Moshe J.; Hessw, Joanne E.; McBlane, J. Fraser Nucleic Acids Research, Vol. 21, Issue 24 https://doi.org/10.1093/nar/21.24.5644	journal	January 1993
Dispensable sequence motifs in the RAG-1 and RAG-2 genes for plasmid V(D)J recombination. Silver, D. P.; Spanopoulou, E.; Mulligan, R. C. Proceedings of the National Academy of Sciences, Vol. 90, Issue 13 https://doi.org/10.1073/pnas.90.13.6100	journal	July 1993
Initial Stages of V(D)J Recombination: The Organization of RAG1/2 and RSS DNA in the Postcleavage Complex Grundy, Gabrielle J.; Ramón-Maiques, Santiago; Dimitriadis, Emilios K. Molecular Cell, Vol. 35, Issue 2 https://doi.org/10.1016/j.molcel.2009.06.022	journal	July 2009
Intermediates in V(D)J recombination: A stable RAG1/2 complex sequesters cleaved RSS ends Jones, J. M.; Gellert, M. Proceedings of the National Academy of Sciences, Vol. 98, Issue 23 https://doi.org/10.1073/pnas.221471198	journal	October 2001
Multi-crystal anomalous diffraction for low-resolution macromolecular phasing Liu, Qun; Zhang, Zhen; Hendrickson, Wayne A. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 1 https://doi.org/10.1107/S0907444910046573	journal	December 2010
RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of ‘alternative NHEJ’ Gigi, Vered; Lewis, Susanna; Shestova, Olga Nucleic Acids Research, Vol. 42, Issue 10 https://doi.org/10.1093/nar/gku295	journal	April 2014
Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis Yin, Fang Fang; Bailey, Scott; Innis, C. Axel Nature Structural & Molecular Biology, Vol. 16, Issue 5 https://doi.org/10.1038/nsmb.1593	journal	April 2009
Identification of Two Catalytic Residues in RAG1 that Define a Single Active Site within the RAG1/RAG2 Protein Complex Fugmann, Sebastian D.; Villey, Isabelle J.; Ptaszek, Leon M. Molecular Cell, Vol. 5, Issue 1 https://doi.org/10.1016/S1097-2765(00)80406-2	journal	January 2000
Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase Kim, D. R.; Dai, Y.; Mundy, C. L. Genes & Development, Vol. 13, Issue 23 https://doi.org/10.1101/gad.13.23.3070	journal	December 1999
Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination Landree, M. A.; Wibbenmeyer, J. A.; Roth, D. B. Genes & Development, Vol. 13, Issue 23 https://doi.org/10.1101/gad.13.23.3059	journal	December 1999
DDE transposases: Structural similarity and diversity Nesmelova, Irina V.; Hackett, Perry B. Advanced Drug Delivery Reviews, Vol. 62, Issue 12 https://doi.org/10.1016/j.addr.2010.06.006	journal	September 2010
The DDE Motif in RAG-1 Is Contributed in trans to a Single Active Site That Catalyzes the Nicking and Transesterification Steps of V(D)J Recombination Swanson, P. C. Molecular and Cellular Biology, Vol. 21, Issue 2 https://doi.org/10.1128/MCB.21.2.449-458.2001	journal	January 2001
A Zinc Site in the C-Terminal Domain of RAG1 Is Essential for DNA Cleavage Activity Gwyn, Lori M.; Peak, Mandy M.; De, Pallabi Journal of Molecular Biology, Vol. 390, Issue 5 https://doi.org/10.1016/j.jmb.2009.05.076	journal	July 2009
A Zinc-binding Domain Involved in the Dimerization of RAG1 Rodgers, Karla K.; Bu, Zimei; Fleming, Karen G. Journal of Molecular Biology, Vol. 260, Issue 1 https://doi.org/10.1006/jmbi.1996.0382	journal	July 1996
Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches Aravind, L.; Koonin, Eugene V. Journal of Molecular Biology, Vol. 287, Issue 5 https://doi.org/10.1006/jmbi.1999.2653	journal	April 1999
The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis Callebaut, I.; Mornon, J. -P. Cellular and Molecular Life Sciences (CMLS), Vol. 54, Issue 8 https://doi.org/10.1007/s000180050216	journal	August 1998
RAG-2 Promotes Heptamer Occupancy by RAG-1 in the Assembly of a V(D)J Initiation Complex Swanson, Patrick C.; Desiderio, Stephen Molecular and Cellular Biology, Vol. 19, Issue 5 https://doi.org/10.1128/MCB.19.5.3674	journal	May 1999
Mutational Analysis of All Conserved Basic Amino Acids in RAG-1 Reveals Catalytic, Step Arrest, and Joining-Deficient Mutants in the V(D)J Recombinase Huye, L. E.; Purugganan, M. M.; Jiang, M. -M. Molecular and Cellular Biology, Vol. 22, Issue 10 https://doi.org/10.1128/MCB.22.10.3460-3473.2002	journal	May 2002
Amino Acid Residues in RAG1 Responsible for the Interaction with RAG2 during the V(D)J Recombination Process Ko, Jung Eun; Kim, Choong Won; Kim, Deok Ryong Journal of Biological Chemistry, Vol. 279, Issue 9 https://doi.org/10.1074/jbc.M311471200	journal	December 2003
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
Structural Basis of hAT Transposon End Recognition by Hermes, an Octameric DNA Transposase from Musca domestica Hickman, Alison B.; Ewis, Hosam E.; Li, Xianghong Cell, Vol. 158, Issue 2 https://doi.org/10.1016/j.cell.2014.05.037	journal	July 2014
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
Molecular Architecture of the Mos1 Paired-End Complex: The Structural Basis of DNA Transposition in a Eukaryote Richardson, Julia M.; Colloms, Sean D.; Finnegan, David J. Cell, Vol. 138, Issue 6 https://doi.org/10.1016/j.cell.2009.07.012	journal	September 2009
Structure/function insights into Tn5 transposition Steiniger-White, Mindy; Rayment, Ivan; Reznikoff, William S. Current Opinion in Structural Biology, Vol. 14, Issue 1 https://doi.org/10.1016/j.sbi.2004.01.008	journal	February 2004
Requirements for DNA hairpin formation by RAG1/2 Grundy, G. J.; Hesse, J. E.; Gellert, M. Proceedings of the National Academy of Sciences, Vol. 104, Issue 9 https://doi.org/10.1073/pnas.0611293104	journal	February 2007
Amino acid residues in Rag1 crucial for DNA hairpin formation Lu, Catherine P.; Sandoval, Hector; Brandt, Vicky L. Nature Structural & Molecular Biology, Vol. 13, Issue 11 https://doi.org/10.1038/nsmb1154	journal	October 2006
The RAG1 Homeodomain Recruits HMG1 and HMG2 To Facilitate Recombination Signal Sequence Binding and To Enhance the Intrinsic DNA-Bending Activity of RAG1-RAG2 Aidinis, Vassilis; Bonaldi, Tiziana; Beltrame, Monica Molecular and Cellular Biology, Vol. 19, Issue 10 https://doi.org/10.1128/MCB.19.10.6532	journal	October 1999
Stimulation of V(D)J cleavage by high mobility group proteins van Gent, D. C. The EMBO Journal, Vol. 16, Issue 10 https://doi.org/10.1093/emboj/16.10.2665	journal	May 1997
Functional Analysis of Coordinated Cleavage in V(D)J Recombination Kim, Deok Ryong; Oettinger, Marjorie A. Molecular and Cellular Biology, Vol. 18, Issue 8 https://doi.org/10.1128/MCB.18.8.4679	journal	August 1998
A time- and cost-efficient system for high-level protein production in mammalian cells Aricescu, A. Radu; Lu, Weixian; Jones, E. Yvonne Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 10 https://doi.org/10.1107/S0907444906029799	journal	September 2006
A RAG-1/RAG-2 Tetramer Supports 12/23-Regulated Synapsis, Cleavage, and Transposition of V(D)J Recombination Signals Swanson, P. C. Molecular and Cellular Biology, Vol. 22, Issue 22 https://doi.org/10.1128/MCB.22.22.7790-7801.2002	journal	November 2002
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
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
Maximum-likelihood density modification Terwilliger, Thomas C. Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 8 https://doi.org/10.1107/S0907444900005072	journal	August 2000
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
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
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Multiple sequence alignment with the Clustal series of programs Chenna, R. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg500	journal	July 2003
Structural and biochemical characterization of the KLHL3–WNK kinase interaction important in blood pressure regulation Schumacher, Frances-Rose; Sorrell, Fiona J.; Alessi, Dario R. Biochemical Journal, Vol. 460, Issue 2 https://doi.org/10.1042/BJ20140153	journal	May 2014
The C-terminal domain of DNA gyrase A adopts a DNA-bending -pinwheel fold Corbett, K. D.; Shultzaberger, R. K.; Berger, J. M. Proceedings of the National Academy of Sciences, Vol. 101, Issue 19 https://doi.org/10.1073/pnas.0401595101	journal	May 2004
Lesson from hypomorphic recombination-activating gene (RAG) mutations: Why asymptomatic siblings should also be tested Schuetz, Catharina; Pannicke, Ulrich; Jacobsen, Eva-Maria Journal of Allergy and Clinical Immunology, Vol. 133, Issue 4 https://doi.org/10.1016/j.jaci.2013.10.021	journal	April 2014
Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B–severe combined immune deficiency or Omenn syndrome Corneo, Barbara; Moshous, Despina; Güngör, Tayfun Blood, Vol. 97, Issue 9 https://doi.org/10.1182/blood.V97.9.2772	journal	May 2001
Severe combined immunodeficiency caused by a new homozygous RAG1 mutation with progressive encephalopathy Dhingra, Nivedita; Yadav, Satya Prakash; de Villartay, Jean-Pierre Hematology/Oncology and Stem Cell Therapy, Vol. 7, Issue 1 https://doi.org/10.1016/j.hemonc.2013.11.001	journal	March 2014
Expression and V(D)J recombination activity of mutated RAG-1 proteins Sadofsky, M. J.; Hesse, J. E.; McBlane, J. F. Nucleic Acids Research, Vol. 22, Issue 3 https://doi.org/10.1093/nar/22.3.550	journal	January 1994
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
A RAG-1/RAG-2 Tetramer Supports 12/23-Regulated Synapsis, Cleavage, and Transposition of V(D)J Recombination Signals Swanson, Patrick C. Molecular and Cellular Biology, Vol. 23, Issue 8 https://doi.org/10.1128/mcb.23.8.3029.2003	journal	April 2003
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

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