1en7 Citations

X-ray structure of T4 endonuclease VII: a DNA junction resolvase with a novel fold and unusual domain-swapped dimer architecture.

EMBO J. 18 1447-58 (1999)
Cited: 77 times
EuropePMC logo PMID: 10075917


Phage T4 endonuclease VII (Endo VII), the first enzyme shown to resolve Holliday junctions, recognizes a broad spectrum of DNA substrates ranging from branched DNAs to single base mismatches. We have determined the crystal structures of the Ca2+-bound wild-type and the inactive N62D mutant enzymes at 2.4 and 2.1 A, respectively. The Endo VII monomers form an elongated, highly intertwined molecular dimer exhibiting extreme domain swapping. The major dimerization elements are two pairs of antiparallel helices forming a novel 'four-helix cross' motif. The unique monomer fold, almost completely lacking beta-sheet structure and containing a zinc ion tetrahedrally coordinated to four cysteines, does not resemble any of the known junction-resolving enzymes, including the Escherichia coli RuvC and lambda integrase-type recombinases. The S-shaped dimer has two 'binding bays' separated by approximately 25 A which are lined by positively charged residues and contain near their base residues known to be essential for activity. These include Asp40 and Asn62, which function as ligands for the bound calcium ions. A pronounced bipolar charge distribution suggests that branched DNA substrates bind to the positively charged face with the scissile phosphates located near the divalent cations. A model for the complex with a four-way DNA junction is presented.

Articles - 1en7 mentioned but not cited (1)

  1. Structural insights into the function of ZRANB3 in replication stress response. Sebesta M, Cooper CDO, Ariza A, Carnie CJ, Ahel D. Nat Commun 8 15847 (2017)

Reviews citing this publication (13)

  1. Holliday junction-resolving enzymes-structures and mechanisms. Lilley DMJ. FEBS Lett. 591 1073-1082 (2017)
  2. Crystallographic studies on protein misfolding: Domain swapping and amyloid formation in the SH3 domain. Cámara-Artigas A. Arch. Biochem. Biophys. 602 116-126 (2016)
  3. Holliday junction resolvases. Wyatt HD, West SC. Cold Spring Harb Perspect Biol 6 a023192 (2014)
  4. New insight into the recognition of branched DNA structure by junction-resolving enzymes. Déclais AC, Lilley DM. Curr. Opin. Struct. Biol. 18 86-95 (2008)
  5. The stacked-X DNA Holliday junction and protein recognition. Khuu PA, Voth AR, Hays FA, Ho PS. J. Mol. Recognit. 19 234-242 (2006)
  6. Happy Hollidays: 40th anniversary of the Holliday junction. Liu Y, West SC. Nat. Rev. Mol. Cell Biol. 5 937-944 (2004)
  7. The unfolding story of three-dimensional domain swapping. Rousseau F, Schymkowitz JW, Itzhaki LS. Structure 11 243-251 (2003)
  8. Bacteriophage T4 genome. Miller ES, Kutter E, Mosig G, Arisaka F, Kunisawa T, Rüger W. Microbiol. Mol. Biol. Rev. 67 86-156 (2003)
  9. Protein folding and three-dimensional domain swapping: a strained relationship? Newcomer ME. Curr. Opin. Struct. Biol. 12 48-53 (2002)
  10. 3D domain swapping: as domains continue to swap. Liu Y, Eisenberg D. Protein Sci. 11 1285-1299 (2002)
  11. The X philes: structure-specific endonucleases that resolve Holliday junctions. Sharples GJ. Mol. Microbiol. 39 823-834 (2001)
  12. The junction-resolving enzymes. Lilley DM, White MF. Nat. Rev. Mol. Cell Biol. 2 433-443 (2001)
  13. Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Chevalier BS, Stoddard BL. Nucleic Acids Res. 29 3757-3774 (2001)

Articles citing this publication (63)

  1. Inference of macromolecular assemblies from crystalline state. Krissinel E, Henrick K. J. Mol. Biol. 372 774-797 (2007)
  2. SURVEY AND SUMMARY: holliday junction resolvases and related nucleases: identification of new families, phyletic distribution and evolutionary trajectories. Aravind L, Makarova KS, Koonin EV. Nucleic Acids Res. 28 3417-3432 (2000)
  3. Imbroglios of viral taxonomy: genetic exchange and failings of phenetic approaches. Lawrence JG, Hatfull GF, Hendrix RW. J. Bacteriol. 184 4891-4905 (2002)
  4. Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system. Aravind L, Koonin EV. Genome Res. 11 1365-1374 (2001)
  5. The Holliday junction in an inverted repeat DNA sequence: sequence effects on the structure of four-way junctions. Eichman BF, Vargason JM, Mooers BH, Ho PS. Proc. Natl. Acad. Sci. U.S.A. 97 3971-3976 (2000)
  6. Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA. Cai M, Huang Y, Ghirlando R, Wilson KL, Craigie R, Clore GM. EMBO J. 20 4399-4407 (2001)
  7. Treble clef finger--a functionally diverse zinc-binding structural motif. Grishin NV. Nucleic Acids Res. 29 1703-1714 (2001)
  8. Structural parsimony in endonuclease active sites: should the number of homing endonuclease families be redefined? Kühlmann UC, Moore GR, James R, Kleanthous C, Hemmings AM. FEBS Lett. 463 1-2 (1999)
  9. The genome of bacteriophage phiKMV, a T7-like virus infecting Pseudomonas aeruginosa. Lavigne R, Burkal'tseva MV, Robben J, Sykilinda NN, Kurochkina LP, Grymonprez B, Jonckx B, Krylov VN, Mesyanzhinov VV, Volckaert G. Virology 312 49-59 (2003)
  10. Characterization of the C-terminal DNA-binding/DNA endonuclease region of a group II intron-encoded protein. San Filippo J, Lambowitz AM. J. Mol. Biol. 324 933-951 (2002)
  11. Crystal structure of the archaeal holliday junction resolvase Hjc and implications for DNA recognition. Nishino T, Komori K, Tsuchiya D, Ishino Y, Morikawa K. Structure 9 197-204 (2001)
  12. Crystal structure of T4 endonuclease VII resolving a Holliday junction. Biertümpfel C, Yang W, Suck D. Nature 449 616-620 (2007)
  13. DNA binding and cleavage by the periplasmic nuclease Vvn: a novel structure with a known active site. Li CL, Hor LI, Chang ZF, Tsai LC, Yang WZ, Yuan HS. EMBO J. 22 4014-4025 (2003)
  14. Structure of Hjc, a Holliday junction resolvase, from Sulfolobus solfataricus. Bond CS, Kvaratskhelia M, Richard D, White MF, Hunter WN. Proc. Natl. Acad. Sci. U.S.A. 98 5509-5514 (2001)
  15. Resolving the relationships of resolving enzymes. Lilley DM, White MF. Proc. Natl. Acad. Sci. U.S.A. 97 9351-9353 (2000)
  16. An equivalent metal ion in one- and two-metal-ion catalysis. Yang W. Nat. Struct. Mol. Biol. 15 1228-1231 (2008)
  17. Polyphyletic evolution of type II restriction enzymes revisited: two independent sources of second-hand folds revealed. Bujnicki JM, Radlinska M, Rychlewski L. Trends Biochem. Sci. 26 9-11 (2001)
  18. The crystal structure of the nuclease domain of colicin E7 suggests a mechanism for binding to double-stranded DNA by the H-N-H endonucleases. Cheng YS, Hsia KC, Doudeva LG, Chak KF, Yuan HS. J. Mol. Biol. 324 227-236 (2002)
  19. HNH family subclassification leads to identification of commonality in the His-Me endonuclease superfamily. Mehta P, Katta K, Krishnaswamy S. Protein Sci. 13 295-300 (2004)
  20. DNA binding and degradation by the HNH protein ColE7. Hsia KC, Chak KF, Liang PH, Cheng YS, Ku WY, Yuan HS. Structure 12 205-214 (2004)
  21. Two recombination-dependent DNA replication pathways of bacteriophage T4, and their roles in mutagenesis and horizontal gene transfer. Mosig G, Gewin J, Luder A, Colowick N, Vo D. Proc. Natl. Acad. Sci. U.S.A. 98 8306-8311 (2001)
  22. Genome of Xanthomonas oryzae bacteriophage Xp10: an odd T-odd phage. Yuzenkova J, Nechaev S, Berlin J, Rogulja D, Kuznedelov K, Inman R, Mushegian A, Severinov K. J. Mol. Biol. 330 735-748 (2003)
  23. Crystal structure of the fission yeast mitochondrial Holliday junction resolvase Ydc2. Ceschini S, Keeley A, McAlister MS, Oram M, Phelan J, Pearl LH, Tsaneva IR, Barrett TE. EMBO J. 20 6601-6611 (2001)
  24. The structure of Bacillus subtilis RecU Holliday junction resolvase and its role in substrate selection and sequence-specific cleavage. McGregor N, Ayora S, Sedelnikova S, Carrasco B, Alonso JC, Thaw P, Rafferty J. Structure 13 1341-1351 (2005)
  25. Metal ions bound at the active site of the junction-resolving enzyme T7 endonuclease I. Hadden JM, Déclais AC, Phillips SE, Lilley DM. EMBO J. 21 3505-3515 (2002)
  26. Two Holliday junction resolving enzymes in Sulfolobus solfataricus. Kvaratskhelia M, White MF. J. Mol. Biol. 297 923-932 (2000)
  27. Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje. Middleton CL, Parker JL, Richard DJ, White MF, Bond CS. Nucleic Acids Res. 32 5442-5451 (2004)
  28. Metal ions and phosphate binding in the H-N-H motif: crystal structures of the nuclease domain of ColE7/Im7 in complex with a phosphate ion and different divalent metal ions. Sui MJ, Tsai LC, Hsia KC, Doudeva LG, Ku WY, Han GW, Yuan HS. Protein Sci. 11 2947-2957 (2002)
  29. A novel protein fold and extreme domain swapping in the dimeric TorD chaperone from Shewanella massilia. Tranier S, Iobbi-Nivol C, Birck C, Ilbert M, Mortier-Barrière I, Méjean V, Samama JP. Structure 11 165-174 (2003)
  30. Holliday junction resolving enzymes of archaeal viruses SIRV1 and SIRV2. Birkenbihl RP, Neef K, Prangishvili D, Kemper B. J. Mol. Biol. 309 1067-1076 (2001)
  31. The conserved asparagine in the HNH motif serves an important structural role in metal finger endonucleases. Huang H, Yuan HS. J. Mol. Biol. 368 812-821 (2007)
  32. Quasi-equivalence in site-specific recombinase structure and function: crystal structure and activity of trimeric Cre recombinase bound to a three-way Lox DNA junction. Woods KC, Martin SS, Chu VC, Baldwin EP. J. Mol. Biol. 313 49-69 (2001)
  33. Crystal structural analysis and metal-dependent stability and activity studies of the ColE7 endonuclease domain in complex with DNA/Zn2+ or inhibitor/Ni2+. Doudeva LG, Huang H, Hsia KC, Shi Z, Li CL, Shen Y, Cheng YS, Yuan HS. Protein Sci. 15 269-280 (2006)
  34. The complex between a four-way DNA junction and T7 endonuclease I. Déclais AC, Fogg JM, Freeman AD, Coste F, Hadden JM, Phillips SE, Lilley DM. EMBO J. 22 1398-1409 (2003)
  35. Research Support, Non-U.S. Gov't The search for a human Holliday junction resolvase. West SC. Biochem. Soc. Trans. 37 519-526 (2009)
  36. The active site of the junction-resolving enzyme T7 endonuclease I. Déclais AC, Hadden J, Phillips SE, Lilley DM. J. Mol. Biol. 307 1145-1158 (2001)
  37. Hjc resolvase is a distantly related member of the type II restriction endonuclease family. Daiyasu H, Komori K, Sakae S, Ishino Y, Toh H. Nucleic Acids Res. 28 4540-4543 (2000)
  38. Biochemical characterization of bacteriophage T4 Mre11-Rad50 complex. Herdendorf TJ, Albrecht DW, Benkovic SJ, Nelson SW. J. Biol. Chem. 286 2382-2392 (2011)
  39. Distortion of DNA junctions imposed by the binding of resolving enzymes: a fluorescence study. Fogg JM, Kvaratskhelia M, White MF, Lilley DM. J. Mol. Biol. 313 751-764 (2001)
  40. Identification of a new subfamily of HNH nucleases and experimental characterization of a representative member, HphI restriction endonuclease. Cymerman IA, Obarska A, Skowronek KJ, Lubys A, Bujnicki JM. Proteins 65 867-876 (2006)
  41. The structure of Escherichia coli RusA endonuclease reveals a new Holliday junction DNA binding fold. Rafferty JB, Bolt EL, Muranova TA, Sedelnikova SE, Leonard P, Pasquo A, Baker PJ, Rice DW, Sharples GJ, Lloyd RG. Structure 11 1557-1567 (2003)
  42. Open interface and large quaternary structure movements in 3D domain swapped proteins: insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease A. Merlino A, Ceruso MA, Vitagliano L, Mazzarella L. Biophys. J. 88 2003-2012 (2005)
  43. RusA proteins from the extreme thermophile Aquifex aeolicus and lactococcal phage r1t resolve Holliday junctions. Sharples GJ, Bolt EL, Lloyd RG. Mol. Microbiol. 44 549-559 (2002)
  44. Identification of a single HNH active site in type IIS restriction endonuclease Eco31I. Jakubauskas A, Giedriene J, Bujnicki JM, Janulaitis A. J. Mol. Biol. 370 157-169 (2007)
  45. NrdH-redoxin of Corynebacterium ammoniagenes forms a domain-swapped dimer. Stehr M, Lindqvist Y. Proteins 55 613-619 (2004)
  46. Holliday junction binding and resolution by the Rap structure-specific endonuclease of phage lambda. Sharples GJ, Curtis FA, McGlynn P, Bolt EL. J. Mol. Biol. 340 739-751 (2004)
  47. The protein gp74 from the bacteriophage HK97 functions as a HNH endonuclease. Moodley S, Maxwell KL, Kanelis V. Protein Sci. 21 809-818 (2012)
  48. Specific recognition of four-way DNA junctions by the C-terminal zinc-binding domain of HPV oncoprotein E6. Ristriani T, Nominé Y, Masson M, Weiss E, Travé G. J. Mol. Biol. 305 729-739 (2001)
  49. Comparison of backbone dynamics of monomeric and domain-swapped stefin A. Japelj B, Waltho JP, Jerala R. Proteins 54 500-512 (2004)
  50. Analysis of conserved basic residues associated with DNA binding (Arg69) and catalysis (Lys76) by the RusA holliday junction resolvase. Bolt EL, Sharples GJ, Lloyd RG. J. Mol. Biol. 304 165-176 (2000)
  51. The major apoptotic endonuclease DFF40/CAD is a deoxyribose-specific and double-strand-specific enzyme. Hanus J, Kalinowska-Herok M, Widlak P. Apoptosis 13 377-382 (2008)
  52. Genome sequence and characterization of a Rhodococcus equi phage REQ1. Petrovski S, Seviour RJ, Tillett D. Virus Genes 46 588-590 (2013)
  53. Multiple Holliday junction resolving enzyme activities in the Crenarchaeota and Euryarchaeota. Kvaratskhelia M, Wardleworth BN, White MF. FEBS Lett. 491 243-246 (2001)
  54. Structural insights into apoptotic DNA degradation by CED-3 protease suppressor-6 (CPS-6) from Caenorhabditis elegans. Lin JL, Nakagawa A, Lin CL, Hsiao YY, Yang WZ, Wang YT, Doudeva LG, Skeen-Gaar RR, Xue D, Yuan HS. J. Biol. Chem. 287 7110-7120 (2012)
  55. Computational studies of the reversible domain swapping of p13suc1. Chahine J, Cheung MS. Biophys. J. 89 2693-2700 (2005)
  56. In silico analysis of mycobacteriophage Che12 genome: characterization of genes required to lysogenise Mycobacterium tuberculosis. Gomathi NS, Sameer H, Kumar V, Balaji S, Dustackeer VN, Narayanan PR. Comput Biol Chem 31 82-91 (2007)
  57. Genetic engineering of Escherichia coli to produce a 1:1 complex of the anabaena sp. PCC 7120 nuclease NucA and its inhibitor NuiA. Korn C, Meiss G, Gast F, Gimadutdinow O, Urbanke C, Pingoud A. Gene 253 221-229 (2000)
  58. The fragment transformation method to detect the protein structural motifs. Lu CH, Lin YS, Chen YC, Yu CS, Chang SY, Hwang JK. Proteins 63 636-643 (2006)
  59. Metal ion binding in the active site of the junction-resolving enzyme T7 endonuclease I in the presence and in the absence of DNA. Freeman AD, Déclais AC, Lilley DM. J. Mol. Biol. 333 59-73 (2003)
  60. Genetic analysis of an archaeal Holliday junction resolvase in Escherichia coli. Bolt EL, Lloyd RG, Sharples GJ. J. Mol. Biol. 310 577-589 (2001)
  61. High affinity of endonuclease VII for the Holliday structure containing one nick ensures productive resolution. Birkenbihl RP, Kemper B. J. Mol. Biol. 321 21-28 (2002)
  62. Analyses of spontaneous mutations of cloned gene 49 of phage T4. Hartung M, Slack M, Kemper B. Mutat. Res. 473 201-210 (2001)
  63. Structural insights into dynamics of RecU-HJ complex formation elucidates key role of NTR and stalk region toward formation of reactive state. Khavnekar S, Dantu SC, Sedelnikova S, Ayora S, Rafferty J, Kale A. Nucleic Acids Res. 45 975-986 (2017)