Crystal structure of SUMO-3-modified thymine-DNA glycosylase
Crystal structure of SUMO-3-modified thymine-DNA glycosylase
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DOI：
10.1016/j.jmb.2006.03.036
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发表时间：
2006-05-26
影响因子：
5.6
通讯作者：
Shirakawa, Masahiro
中科院分区：
文献类型：
--
作者：
Baba, Daichi;Maita, Nobuo;Shirakawa, Masahiro
小的泛素样修饰物SUMO修饰细胞蛋白在调节各种细胞事件中起重要作用。许多不同的核蛋白被SUMO靶向，这种修饰的功能后果是多种多样的。然而，对于大多数蛋白质，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糖基酶（TDG）的偶联诱导TDG与其产物DNA的解离。先前对与SUMO-1偶联的TDG中心区域的结构测定表明，SUMO-1诱导的TDG c端区域构象变化释放了TDG与其产物DNA的紧密结合的机制。在这里，我们确定了与SUMO-3共轭的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SUMO-3共轭TDG的整体结构与先前报道的SUMO-1共轭TDG的结构相似。这两种结构揭示了类似于sumo结合基序（SBM）的TDG序列可以与SUMO-1或SUMO-3形成分子间β -sheet。与典型SBM的结构比较表明，这种类似SBM的TDG序列保留了SBM的所有特征相互作用，表明SBM中的序列多样性。(c) 2006 Elsevier Ltd.版权所有。
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. (c) 2006 Elsevier Ltd. All rights reserved.