The covalent attachment of SUMO (small ubiquitin-related modifier)-family proteins to target proteins is known be involved in various cellular processes. In DNA mismatch repair, uracil/thymine DNA glycosylase (TDG) releases thymine or uracil from G·T and G·U mismatches and remains stably bound to the resulting abasic site until it is transferred to the next enzyme in the repair pathway. SUMO conjugation to TDG promotes its release from the abasic site, and the 2.1-Å-resolution crystal structure of the central region of human TDG conjugated to SUMO-1 shows how this occurs.
The structure, described by Shirakawa and colleagues in Nature, is comprised of two domains — the catalytic core domain of TDG and a SUMO-containing domain that consists of SUMO-1 and the C-terminal region of TDG. No significant structural rearrangements are induced in the TDG core domain or in SUMO-1 by SUMO conjugation. The interesting feature is the complex interface, which contains a covalent interaction (the conjugation site) and non-covalent interactions (an intermolecular β-sheet pairing). The formation of these interactions causes an α-helix of TDG, which is located between them, to protrude from the surface of the complex, such that it would sterically clash with bound DNA. Both the covalent and non-covalent contacts seem to be essential for TDG dissociation from DNA. This work has provided insights into how SUMO modifications function, and has indicated how SUMO proteins might interact with other proteins in a non-covalent manner. REFERENCE Baba, D. et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 435, 979–982 (2005)
This is a preview of subscription content, access via your institution