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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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.
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.
Electron density map of SUMO1-TDG (DOC 745 kb)
Limited proteolysis of TDG and SUMO1-TDG (DOC 539 kb)
DNA and SUMO-1 binding activity of the full-length TDG (DOC 1491 kb)
Data collection and model refinement statistics (DOC 45 kb)
Protein expression and purification (DOC 26 kb)
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Baba, D., Maita, N., Jee, J. et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 435, 979–982 (2005). https://doi.org/10.1038/nature03634
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