Structural and functional studies of SUMO ylation and poly-ubiquitination

SUMO （Small ubiquitin-like modifier）家族蛋白的附着是一种翻译后修饰，可调节修饰蛋白的功能、结构或定位，并调节大量细胞功能，如转录、DNA修复和染色质结构的调节。靶蛋白之一，胸腺嘧啶DNA糖基酶（TDG）是一种DNA糖基酶，被认为是从含有G-U或G-T碱基对的DNA中剔除错配碱基。已经提出了TDG的SUMO-1或SUMO-2/3连接，以促进其与含有碱基位点的DNA分离。我们已经确定了TDG的中心区域的晶体结构，包括催化核心结构域和SUMOylation位点，共轭到SUMO-1 （SUMO-1-TDG）或SUMO-3 （SUMO-3-TDG）。SUMO-1-TDG的结构表明，TDG的中心区域通过共价和非共价接触与SUMO-1相互作用，这似乎导致了TDG区域的结构重排。模型的建立假设这种可能的结构变化可能会在蛋白质表面产生一个突起，它的定位是为了与与TDG结合的DNA发生空间冲突。SUMO-3-TDG的结构与SUMO-1-TDG相似。

Attachment of SUMO (Small ubiquitin-like modifier) family proteins is a post-translational modification that regulates the functions, structures or localizations of modified proteins, and regulates a vast arrays of cellular functions, such as transcription, DNA repair and regulation of chromatin structures. One of the target proteins, Thymine DNA glycosylase (TDG) is an DNA glycosylase that is thought to excise mismatch base from DNA containing G-U or G-T base pairs. SUMO-1 or SUMO-2/3 attachment of TDG has been proposed to promote its dissociation from DNA containing an abasic site.We have determined the crystal structure of the central region of TDG, which involves the catalytic core domain and the SUMOylation site, conjugated to SUMO-1 (SUMO-1-TDG) or SUMO-3 (SUMO-3-TDG). The structure of SUMO-1-TDG shows that the central region of TDG interacts SUMO-1 through both covalent and non-covalent contacts, which seemingly induces a structural rearrangement in a region of TDG. A model building assumes that this possible structural change may create a protrusion on the protein surface, which is positioned so as to make a steric clash with DNA bound to TDG. The structure of SUMO-3-TDG is similar to that of SUMO-1-TDG.