title: Crystal structure of SUMO-3-modified thymine-DNA glycosylase.
abstract: Modification of cellular proteins by the small ubiquitin-like modifier SUMO is important in regulating various cellular events. Many different nuclear proteins are targeted by SUMO, and the functional consequences of this modification are diverse. For most proteins, however, the functional and structural consequences of modification by specific SUMO isomers are unclear. Conjugation of SUMO to thymine-DNA glycosylase (TDG) induces the dissociation of TDG from its product DNA. Structure determination of the TDG central region conjugated to SUMO-1 previously suggested a mechanism in which the SUMOylation-induced conformational change in the C-terminal region of TDG releases TDG from tight binding to its product DNA. Here, we have determined the crystal structure of the central region of TDG conjugated to SUMO-3. The overall structure of SUMO-3-conjugated TDG is similar to the previously reported structure of TDG conjugated to SUMO-1, despite the relatively low level of amino acid sequence similarity between SUMO-3 and SUMO-1. The two structures revealed that the sequence of TDG that resembles the SUMO-binding motif (SBM) can form an intermolecular beta-sheet with either SUMO-1 or SUMO-3. Structural comparison with the canonical SBM shows that this SBM-like sequence of TDG retains all of the characteristic interactions of the SBM, indicating sequence diversity in the SBM.
authors.affiliation: Graduate School of Integrated Science, Yokohama City University, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Baba
authors.forename: Nobuo
authors.initials: N
authors.lastname: Maita
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Jee
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uchimura
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Hidehito
authors.initials: H
authors.lastname: Tochio
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Hiroaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirakawa
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics; D050828:Protein Inhibitors of Activated STAT / Q000737:chemistry / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D044502:Thymine DNA Glycosylase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D020033:Protein Isoforms; C492189:SUMO3 protein, human; D014452:Ubiquitins; C094493:ran-binding protein 2; D044502:Thymine DNA Glycosylase