Baba Daichi, Maita Nobuo, Jee Jun-Goo, Uchimura Yasuhiro, Saitoh Hisato, Sugasawa Kaoru, Hanaoka Fumio, Tochio Hidehito, Hiroaki Hidekazu, Shirakawa Masahiro
Graduate School of Integrated Science, Yokohama City University, Japan.
J Mol Biol. 2006 May 26;359(1):137-47. doi: 10.1016/j.jmb.2006.03.036. Epub 2006 Mar 31.
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.
小泛素样修饰物SUMO对细胞蛋白质的修饰在调节各种细胞事件中很重要。许多不同的核蛋白都以SUMO为靶点，这种修饰的功能后果多种多样。然而，对于大多数蛋白质来说，特定SUMO异构体修饰的功能和结构后果尚不清楚。SUMO与胸腺嘧啶-DNA糖基化酶（TDG）的缀合会诱导TDG与其产物DNA解离。先前确定的与SUMO-1缀合的TDG中心区域的结构表明了一种机制，即TDG C末端区域中SUMO化诱导的构象变化使TDG从与产物DNA的紧密结合中释放出来。在这里，我们确定了与SUMO-3缀合的TDG中心区域的晶体结构。尽管SUMO-3和SUMO-1之间的氨基酸序列相似性相对较低，但与SUMO-3缀合的TDG的整体结构与先前报道的与SUMO-1缀合的TDG结构相似。这两种结构表明，TDG中类似于SUMO结合基序（SBM）的序列可以与SUMO-1或SUMO-3形成分子间β-折叠。与典型SBM的结构比较表明，TDG的这种SBM样序列保留了SBM的所有特征相互作用，表明SBM中存在序列多样性。
