Crystal structure of thymine DNA glycosylase conjugated to SUMO-1 (original) (raw)
- Letter
- Published: 16 June 2005
- Nobuo Maita1,2,
- Jun-Goo Jee3 nAff10,
- Yasuhiro Uchimura4,
- Hisato Saitoh4,
- Kaoru Sugasawa5,6,
- Fumio Hanaoka5,6,7,
- Hidehito Tochio1,
- Hidekazu Hiroaki1 &
- …
- Masahiro Shirakawa1,3,8,9
Nature volume 435, pages 979–982 (2005)Cite this article
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Abstract
Members of the small ubiquitin-like modifier (SUMO) family can be covalently attached to the lysine residue of a target protein through an enzymatic pathway similar to that used in ubiquitin conjugation1, and are involved in various cellular events that do not rely on degradative signalling via the proteasome or lysosome2,3,4,5. However, little is known about the molecular mechanisms of SUMO-modification-induced protein functional transfer. During DNA mismatch repair, SUMO conjugation of the uracil/thymine DNA glycosylase TDG promotes the release of TDG from the abasic (AP) site created after base excision, and coordinates its transfer to AP endonuclease 1, which catalyses the next step in the repair pathway6. Here we report the crystal structure of the central region of human TDG conjugated to SUMO-1 at 2.1 Å resolution. The structure reveals a helix protruding from the protein surface, which presumably interferes with the product DNA and thus promotes the dissociation of TDG from the DNA molecule. This helix is formed by covalent and non-covalent contacts between TDG and SUMO-1. The non-covalent contacts are also essential for release from the product DNA, as verified by mutagenesis.
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References
- Johnson, E. S. Protein modification by SUMO. Annu. Rev. Biochem. 73, 355–382 (2004)
Article CAS Google Scholar - Gill, G. SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev. 18, 2046–2059 (2004)
Article CAS Google Scholar - Seeler, J. S. & Dejean, A. Nuclear and unclear functions of SUMO. Nature Rev. Mol. Cell Biol. 4, 690–699 (2003)
Article CAS Google Scholar - Kim, K. I., Baek, S. H. & Chung, C. H. Versatile protein tag, SUMO: its enzymology and biological function. J. Cell. Physiol. 191, 257–268 (2002)
Article CAS Google Scholar - Mahajan, R., Delphin, C., Guan, T., Gerace, L. & Melchior, F. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88, 97–107 (1997)
Article CAS Google Scholar - Hardeland, U. et al. Thymine DNA glycosylase. Prog. Nucleic Acid Res. Mol. Biol. 68, 235–253 (2001)
Article CAS Google Scholar - Waters, T. R. & Swann, P. F. Kinetics of the action of thymine DNA glycosylase. J. Biol. Chem. 273, 20007–20014 (1998)
Article CAS Google Scholar - Waters, T. R., Gallinari, P., Jiricny, J. & Swann, P. F. Human thymine DNA glycosylase binds to apurinic sites in DNA but is displaced by human apurinic endonuclease 1. J. Biol. Chem. 274, 67–74 (1999)
Article CAS Google Scholar - Hardeland, U., Steinacher, R., Jiricny, J. & Schar, P. Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. EMBO J. 21, 1456–1464 (2002)
Article CAS Google Scholar - Barrett, T. E. et al. Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions. Cell 92, 117–129 (1998)
Article CAS Google Scholar - Hardeland, U., Bentele, M., Jiricny, J. & Schar, P. Separating substrate recognition from base hydrolysis in human thymine DNA glycosylase by mutational analysis. J. Biol. Chem. 275, 33449–33456 (2000)
Article CAS Google Scholar - Roberts, R. J. On base flipping. Cell 82, 9–12 (1995)
Article CAS Google Scholar - Mol, C. D. et al. Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA. Cell 82, 701–708 (1995)
Article CAS Google Scholar - Mol, C. D. et al. Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis. Cell 80, 869–878 (1995)
Article CAS Google Scholar - Bayer, P. et al. Structure determination of the small ubiquitin-related modifier SUMO-1. J. Mol. Biol. 280, 275–286 (1998)
Article CAS Google Scholar - Song, J., Durrin, L. K., Wilkinson, T. A., Krontiris, T. G. & Chen, Y. Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc. Natl Acad. Sci. USA 101, 14373–14378 (2004)
Article ADS CAS Google Scholar - Uchimura, Y., Nakamura, M., Sugasawa, K., Nakao, M. & Saitoh, H. Overproduction of eukaryotic SUMO-1- and SUMO-2-conjugated proteins in Escherichia coli. Anal. Biochem. 331, 204–206 (2004)
Article CAS Google Scholar - Leslie, A. G. Integration of macromolecular diffraction data. Acta Crystallogr. D 55, 1696–1702 (1999)
Article CAS Google Scholar - Collaborative Computational Project No. 4, The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760–763 (1994)
Article Google Scholar - Vagin, A. & Teplyakov, A. MOLREP: an automated program for molecular replacement. J. Appl. Crystallogr. 30, 1022–1025 (1997)
Article CAS Google Scholar - Mossessova, E. & Lima, C. D. Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast. Mol. Cell 5, 865–876 (2000)
Article CAS Google Scholar - Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110–119 (1991)
Article Google Scholar - Brunger, A. T. et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D 54, 905–921 (1998)
Article CAS Google Scholar - DeLano, W. L. PyMOLhttp://www.pymol.org (2002).
- Barrett, T. E. et al. Crystal structure of a thwarted mismatch glycosylase DNA repair complex. EMBO J. 18, 6599–6609 (1999)
Article CAS Google Scholar
Acknowledgements
This work was supported by grants to M.S. from the Japanese Ministry of Education, Science, Sports and Culture, and Japan Science and Technology Agency.
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Author notes
- Jun-Goo Jee
Present address: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA
Authors and Affiliations
- Graduate School of Integrated Science, Yokohama City University, Yokohama, 230-0045, Japan
Daichi Baba, Nobuo Maita, Hidehito Tochio, Hidekazu Hiroaki & Masahiro Shirakawa - Japan Biological Informatics Consortium, Tokyo, 104-0032, Japan
Nobuo Maita - RIKEN Genomic Sciences Center, Yokohama, Kanagawa, 230-0045, Japan
Jun-Goo Jee & Masahiro Shirakawa - Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, 860-0811, Japan
Yasuhiro Uchimura & Hisato Saitoh - Cellular Physiology Laboratory, Discovery Research Institute, RIKEN, Wako, 351-0198, Japan
Kaoru Sugasawa & Fumio Hanaoka - SORST, Japan Science and Technology Agency, 332-0012, Saitama, Kawaguchi, Japan
Kaoru Sugasawa & Fumio Hanaoka - Graduate School of Frontier Biosciences, Osaka University, Suita, 565-0871, Japan
Fumio Hanaoka - Graduate School of Engineering, Kyoto University, Kyoto, 615-8510, Japan
Masahiro Shirakawa - CREST, Japan Science and Technology Corporation, Kawaguchi, 332-0012, Saitama, Japan
Masahiro Shirakawa
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Correspondence toMasahiro Shirakawa.
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Atomic coordinates of SUMO-1–TDG have been deposited in the Protein Data Bank under the accession number 1WYW. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
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Baba, D., Maita, N., Jee, JG. et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1.Nature 435, 979–982 (2005). https://doi.org/10.1038/nature03634
- Received: 06 December 2004
- Accepted: 14 April 2005
- Issue Date: 16 June 2005
- DOI: https://doi.org/10.1038/nature03634
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