Defects in DNA degradation revealed in crystal structures of TREX1 exonuclease mutations linked to autoimmune disease

DNA Repair

Volumn 11, Issue 1, 2012, Pages 65-73

  Bailey, Suzanna L ^a   Harvey, Scott ^a   Perrino, Fred W ^a   Hollis, Thomas ^a  

^a WAKE FOREST UNIVERSITY HEALTH SCIENCES   (United States)

Author keywords

Autoimmune disease; Enzyme mechanism; Exonuclease; Lupus; Protein structure; TREX1

Indexed keywords

ALPHA INTERFERON; APOPROTEIN; DNA ANTIBODY; DOUBLE STRANDED DNA; EXONUCLEASE; GENOMIC DNA; GRANZYME A; HISTIDINE; HOMODIMER; MUTANT PROTEIN; PROTEIN TREX 1; UNCLASSIFIED DRUG;

AICARDI GOUTIERES SYNDROME; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CATALYSIS; CELL DEATH; CONTROLLED STUDY; CRYSTAL STRUCTURE; DISEASE ASSOCIATION; DNA DEGRADATION; ENDOPLASMIC RETICULUM; ENZYME ACTIVE SITE; ENZYME CONFORMATION; ENZYME STRUCTURE; LUPUS ERYTHEMATOSUS; MOUSE; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; X RAY CRYSTALLOGRAPHY;

ANIMALS; APOPROTEINS; AUTOIMMUNE DISEASES; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; DNA DAMAGE; ENZYME STABILITY; EXODEOXYRIBONUCLEASES; HUMANS; HYDROLYSIS; METALS; MICE; MODELS, MOLECULAR; MUTANT PROTEINS; MUTATION; NUCLEIC ACIDS; PHOSPHOPROTEINS; PROTEIN STRUCTURE, SECONDARY;

EID: 84855352447     PISSN: 15687864     EISSN: 15687856     Source Type: Journal    
DOI: 10.1016/j.dnarep.2011.10.007     Document Type: Article

References (57)

1. Mazur D.J., Perrino F.W. Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-5' exonucleases. J. Biol. Chem. 1999, 274:19655-19660.
2. Hoss M., Robins P., Naven T.J., Pappin D.J., Sgouros J., Lindahl T. A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein. EMBO J. 1999, 18:3868-3875.
3. Chowdhury D., Beresford P.J., Zhu P., Zhang D., Sung J.S., Demple B., Perrino F.W., Lieberman J. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol. Cell 2006, 23:133-142.
4. Stetson D.B., Ko J.S., Heidmann T., Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 2008, 134:587-598.
5. Lindahl T., Barnes D.E., Yang Y.G., Robins P. Biochemical properties of mammalian TREX1 and its association with DNA replication and inherited inflammatory disease. Biochem. Soc. Trans. 2009, 37:535-538.
6. Yang Y.G., Lindahl T., Barnes D.E. Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. Cell 2007, 131:873-886.
7. Crow Y.J., Hayward B.E., Parmar R., Robins P., Leitch A., Ali M., Black D.N., van Bokhoven H., Brunner H.G., Hamel B.C., Corry P.C., Cowan F.M., Frints S.G., Klepper J., Livingston J.H., Lynch S.A., Massey R.F., Meritet J.F., Michaud J.L., Ponsot G., Voit T., Lebon P., Bonthron D.T., Jackson A.P., Barnes D.E., Lindahl T. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nat. Genet. 2006, 38:917-920.
8. de Vries B., Steup-Beekman G., Haan J., Bollen E., Luyendijk J., Frants R., Terwindt G., van Buchem M., Huizinga T., van den Maagdenberg A., Ferrari M. TREX1 gene variant in neuropsychiatric systemic lupus erythematosus. Ann. Rheum. Dis. 2009.
9. Gunther C., Meurer M., Stein A., Viehweg A., Lee-Kirsch M.A. Familial chilblain lupus - a monogenic form of cutaneous lupus erythematosus due to a heterozygous mutation in TREX1. Dermatology (Basel, Switzerland) 2009.
10. Hur J.W., Sung Y.K., Shin H.D., Park B.L., Cheong H.S., Bae S.C. TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus. Rheumatol. Int. 2008, 28:783-789.
11. Lee-Kirsch M.A., Chowdhury D., Harvey S., Gong M., Senenko L., Engel K., Pfeiffer C., Hollis T., Gahr M., Perrino F.W., Lieberman J., Hubner N. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J. Mol. Med. (Berlin, Germany) 2007, 85:531-537.
12. Lee-Kirsch M.A., Gong M., Chowdhury D., Senenko L., Engel K., Lee Y.A., de Silva U., Bailey S.L., Witte T., Vyse T.J., Kere J., Pfeiffer C., Harvey S., Wong A., Koskenmies S., Hummel O., Rohde K., Schmidt R.E., Dominiczak A.F., Gahr M., Hollis T., Perrino F.W., Lieberman J., Hubner N. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat. Genet. 2007, 39:1065-1067.
13. Rice G., Newman W.G., Dean J., Patrick T., Parmar R., Flintoff K., Robins P., Harvey S., Hollis T., O'Hara A., Herrick A.L., Bowden A.P., Perrino F.W., Lindahl T., Barnes D.E., Crow Y.J. Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. Am. J. Hum. Genet. 2007, 80:811-815.
14. Richards A., van den Maagdenberg A.M., Jen J.C., Kavanagh D., Bertram P., Spitzer D., Liszewski M.K., Barilla-Labarca M.L., Terwindt G.M., Kasai Y., McLellan M., Grand M.G., Vanmolkot K.R., de Vries B., Wan J., Kane M.J., Mamsa H., Schafer R., Stam A.H., Haan J., de Jong P.T., Storimans C.W., van Schooneveld M.J., Oosterhuis J.A., Gschwendter A., Dichgans M., Kotschet K.E., Hodgkinson S., Hardy T.A., Delatycki M.B., Hajj-Ali R.A., Kothari P.H., Nelson S.F., Frants R.R., Baloh R.W., Ferrari M.D., Atkinson J.P. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat. Genet. 2007, 39:1068-1070.
15. Morita M., Stamp G., Robins P., Dulic A., Rosewell I., Hrivnak G., Daly G., Lindahl T., Barnes D.E. Gene-targeted mice lacking the Trex1 (DNase III) 3'-5' DNA exonuclease develop inflammatory myocarditis. Mol. Cell. Biol. 2004, 24:6719-6727.
16. Crow Y.J., Livingston J.H. Aicardi-Goutieres syndrome: an important Mendelian mimic of congenital infection. Dev. Med. Child Neurol. 2008, 50:410-416.
17. Jepps H., Seal S., Hattingh L., Crow Y.J. The neonatal form of Aicardi-Goutieres syndrome masquerading as congenital infection. Early Hum. Dev. 2008, 84:783-785.
18. Stephenson J.B. Aicardi-Goutieres syndrome (AGS). Eur. J. Paediatr. Neurol. 2008, 12:355-358.
19. Crow Y.J., Rehwinkel J. Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Hum. Mol. Genet. 2009, 18:R130-R136.
20. Rice G., Patrick T., Parmar R., Taylor C.F., Aeby A., Aicardi J., Artuch R., Montalto S.A., Bacino C.A., Barroso B., Baxter P., Benko W.S., Bergmann C., Bertini E., Biancheri R., Blair E.M., Blau N., Bonthron D.T., Briggs T., Brueton L.A., Brunner H.G., Burke C.J., Carr I.M., Carvalho D.R., Chandler K.E., Christen H.J., Corry P.C., Cowan F.M., Cox H., D'Arrigo S., Dean J., De Laet C., De Praeter C., Dery C., Ferrie C.D., Flintoff K., Frints S.G., Garcia-Cazorla A., Gener B., Goizet C., Goutieres F., Green A.J., Guet A., Hamel B.C., Hayward B.E., Heiberg A., Hennekam R.C., Husson M., Jackson A.P., Jayatunga R., Jiang Y.H., Kant S.G., Kao A., King M.D., Kingston H.M., Klepper J., van der Knaap M.S., Kornberg A.J., Kotzot D., Kratzer W., Lacombe D., Lagae L., Landrieu P.G., Lanzi G., Leitch A., Lim M.J., Livingston J.H., Lourenco C.M., Lyall E.G., Lynch S.A., Lyons M.J., Marom D., McClure J.P., McWilliam R., Melancon S.B., Mewasingh L.D., Moutard M.L., Nischal K.K., Ostergaard J.R., Prendiville J., Rasmussen M., Rogers R.C., Roland D., Rosser E.M., Rostasy K., Roubertie A., Sanchis A., Schiffmann R., Scholl-Burgi S., Seal S., Shalev S.A., Corcoles C.S., Sinha G.P., Soler D., Spiegel R., Stephenson J.B., Tacke U., Tan T.Y., Till M., Tolmie J.L., Tomlin P., Vagnarelli F., Valente E.M., Van Coster R.N., Van der Aa N., Vanderver A., Vles J.S., Voit T., Wassmer E., Weschke B., Whiteford M.L., Willemsen M.A., Zankl A., Zuberi S.M., Orcesi S., Fazzi E., Lebon P., Crow Y.J. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am. J. Hum. Genet. 2007, 81:713-725.
21. Hedrich C.M., Fiebig B., Hauck F.H., Sallmann S., Hahn G., Pfeiffer C., Heubner G., Lee-Kirsch M.A., Gahr M. Chilblain lupus erythematosus - a review of literature. Clin. Rheumatol. 2008, 27:1341.
22. de Silva U., Choudhury S., Bailey S.L., Harvey S., Perrino F.W., Hollis T. The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering. J. Biol. Chem. 2007, 282:10537-10543.
23. Brucet M., Querol-Audi J., Serra M., Ramirez-Espain X., Bertlik K., Ruiz L., Lloberas J., Macias M.J., Fita I., Celada A. Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW domains. J. Biol. Chem. 2007, 282:14547-14557.
24. Kirby T.W., Harvey S., DeRose E.F., Chalov S., Chikova A.K., Perrino F.W., Schaaper R.M., London R.E., Pedersen L.C. Structure of the Escherichia coli DNA polymerase III epsilon-HOT proof reading complex. J. Biol. Chem. 2006, 281:38466-38471.
25. Cisneros G.A., Perera L., Schaaper R.M., Pedersen L.C., London R.E., Pedersen L.G., Darden T.A. Reaction mechanism of the epsilon subunit of E. coli DNA polymerase III: insights into active site metal coordination and catalytically significant residues. J. Am. Chem. Soc. 2009, 131:1550-1556.
26. Perrino F.W., de Silva U., Harvey S., Pryor E.E., Cole D.W., Hollis T. Cooperative DNA binding and communication across the dimer interface in the TREX2 3'-5' exonuclease. J. Biol. Chem. 2008.
27. Perrino F.W., Harvey S., McMillin S., Hollis T. The human TREX2 3'-5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis. J. Biol. Chem. 2005, 280:15212-15218.
28. Lehtinen D.A., Harvey S., Mulcahy M.J., Hollis T., Perrino F.W. The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease. J. Biol. Chem. 2008, 283:31649-31656.
29. Fye J.M., Orebaugh C.D., Coffin S.R., Hollis T., Perrino F.W. TREX1 dominant mutations in lupus and Aicardi-Goutieres syndrome. J. Biol. Chem. 2011.
30. Otwinowski W., Minor Z. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997, 276:307-326.
31. Pflugrath J.W. The finer things in X-ray diffraction data collection. Acta Crystallogr. D: Biol. Crystallogr. 1999, 55:1718-1725.
32. McCoy A.J., Grosse-Kunstleve R.W., Adams P.D., Winn M.D., Storoni L.C., Read R.J. Phaser crystallographic software. J. Appl. Crystallogr. 2007, 40:658-674.
33. Emsley P., Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D: Biol. Crystallogr. 2004, 60:2126-2132.
34. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., Jiang J.S., Kuszewski J., Nilges M., Pannu N.S., Read R.J., Rice L.M., Simonson T., Warren G.L. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D: Biol. Crystallogr. 1998, 54(Pt 5):905-921.
35. Murshudov G.N., Vagin A.A., Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D: Biol. Crystallogr. 1997, 53:240-255.
36. Adams P.D., Grosse-Kunstleve R.W., Hung L.W., Ioerger T.R., McCoy A.J., Moriarty N.W., Read R.J., Sacchettini J.C., Sauter N.K., Terwilliger T.C. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D: Biol. Crystallogr. 2002, 58:1948-1954.
37. Painter J., Merritt E.A. Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr. D: Biol. Crystallogr. 2006, 62:439-450.
38. Painter J., Merritt E.A. TLSMD web server for the generation of multi-group TLS models. J. Appl. Crystallogr. 2006, 39:109-111.
39. Davis I.W., Leaver-Fay A., Chen V.B., Block J.N., Kapral G.J., Wang X., Murray L.W., Arendall W.B., Snoeyink J., Richardson J.S., Richardson D.C. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 2007, 35:W375-W383.
40. DeLano W.L. The PyMol Molecular Graphics System 2002, Delano Scientific, Palo Alto, California.
41. Beese L.S., Steitz T.A. Structural basis for the 3'-5' exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism. EMBO J. 1991, 10:25-33.
42. Brautigam C.A., Aschheim K., Steitz T.A. Structural elucidation of the binding and inhibitory properties of lanthanide (III) ions at the 3'-5' exonucleolytic active site of the Klenow fragment. Chem. Biol. 1999, 6:901-908.
43. Derbyshire V., Freemont P.S., Sanderson M.R., Beese L., Friedman J.M., Joyce C.M., Steitz T.A. Genetic and crystallographic studies of the 3',5'-exonucleolytic site of DNA polymerase I. Science 1988, 240:199-201.
44. Hamdan S., Carr P.D., Brown S.E., Ollis D.L., Dixon N.E. Structural basis for proofreading during replication of the Escherichia coli chromosome. Structure (Camb) 2002, 10:535-546.
45. Nowotny M., Yang W. Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. EMBO J. 2006, 25:1924-1933.
46. Mol C.D., Izumi T., Mitra S., Tainer J.A. DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination. Nature 2000, 403:451-456.
47. Viadiu H., Aggarwal A.K. The role of metals in catalysis by the restriction endonuclease BamHI. Nat. Struct. Biol. 1998, 5:910-916.
48. Steitz T.A., Steitz J.A. A general two-metal-ion mechanism for catalytic RNA. Proc. Natl. Acad. Sci. U. S. A. 1993, 90:6498-6502.
49. Orebaugh C.D., Fye J.M., Harvey S., Hollis T., Perrino F.W. The TREX1 exonuclease R114H mutation in Aicardi-Goutieres syndrome and lupus reveals dimeric structure requirements for DNA degradation activity. J. Biol. Chem. 2011, Sep 21. [Epub ahead of print].
50. Breyer W.A., Matthews B.W. Structure of Escherichia coli exonuclease I suggests how processivity is achieved. Nat. Struct. Biol. 2000, 7:1125-1128.
51. Zuo Y., Deutscher M.P. Mechanism of action of RNase T. II. A structural and functional model of the enzyme. J. Biol. Chem. 2002, 277:50160-50164.
52. +-ion catalysis and substrate specificity. Mol. Cell 2006, 22:5-13.
53. De Vivo M., Dal Peraro M., Klein M.L. Phosphodiester cleavage in ribonuclease H occurs via an associative two-metal-aided catalytic mechanism. J. Am. Chem. Soc. 2008, 130:10955-10962.
54. Yang W. An equivalent metal ion in one- and two-metal-ion catalysis. Nat. Struct. Mol. Biol. 2008, 15:1228-1231.
55. Batra V.K., Beard W.A., Shock D.D., Krahn J.M., Pedersen L.C., Wilson S.H. Magnesium-induced assembly of a complete DNA polymerase catalytic complex. Structure 2006, 14:757-766.
56. Horton N.C., Perona J.J. DNA cleavage by EcoRV endonuclease: two metal ions in three metal ion binding sites. Biochemistry 2004, 43:6841-6857.
57. Mazur D.J., Perrino F.W. Excision of 3' termini by the Trex1 and TREX2 3'-5' exonucleases. Characterization of the recombinant proteins. J. Biol. Chem. 2001, 276:17022-17029.