Crystal structure of thymine DNA glycosylase conjugated to SUMO-1.
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 conjugation, and are involved in various cellular events that do not rely on degradative signalling via the proteasome or lysosome. 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 pathway. Here we report the crystal structure of the central region of human TDG conjugated to SUMO-1 at 2.1 A 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.
Baba
Daichi
D
Graduate School of Integrated Science, Yokohama City University, Yokohama 230-0045, Japan.
Maita
Nobuo
N
Jee
Jun-Goo
JG
Uchimura
Yasuhiro
Y
Saitoh
Hisato
H
Sugasawa
Kaoru
K
Hanaoka
Fumio
F
Tochio
Hidehito
H
Hiroaki
Hidekazu
H
Shirakawa
Masahiro
M
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics; D025842:SUMO-1 Protein / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D044502:Thymine DNA Glycosylase / Q000737:chemistry* / Q000378:metabolism*
D025842:SUMO-1 Protein; D004247:DNA; D044502:Thymine DNA Glycosylase