Structural and functional studies of SUMO ylation and poly-ubiquitination

SUMO化和多聚泛素化的结构和功能研究

• 批准号: 16370052
• 负责人: SHIRAKAWA Masahiro
• 金额: $ 9.6万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16370052/
• 关键词: SUMO; protein modification; DNA repair; protein structure determination; X-ray crystallography; ユビキチン; ポリユビキチン; NMR; 立体構造

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.

SUMO（Small ubiquitin-like modifier）家族蛋白的连接是一种翻译后修饰，其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。胸腺嘧啶DNA糖基化酶（Thymine DNA glycosylase，TDG）是一种DNA糖基化酶，被认为是从含有G-U或G-T碱基对的DNA中切除错配碱基。本文报道了SUMO-1（SUMO-1-TDG）或SUMO-3（SUMO-3-TDG）与TDG结合后的晶体结构。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，这似乎诱导了TDG区域的结构重排。一个模型的建立假设，这种可能的结构变化可能会产生一个突出的蛋白质表面上，这是定位，以便使一个空间碰撞与DNA结合TDG。SUMO-3-TDG的结构与SUMO-1-TDG的结构相似。

项目成果

Backbone (l)H, (13)C, and (15) B, coli nickel binding protein NikA.

主链(1)H、(13)C和(15)B，大肠杆菌镍结合蛋白NikA。

• 发表时间: 2005
• 期刊: J Biomolecular NMR 32
• 作者: Rajesh;S.;Heddle;J. G.;Kurashima-Ito;K;Nietlispach;D.;Shirakawa. M.. Tame;J. R.;Ito;Y.
• 通讯作者: Y.

K.-I. The UBL-UBA protein KPC2 is required for degradation of p27 at Gl phase.

K.-I。

• 发表时间: 2005
• 期刊: Molecular and Cellular Biology 25
• 作者: Hara;T.;Kamura;T.;Kotoshiba;S.;Fujiwara;K.;Onoyama;I.;Shirakawa;M.;Nakayama
• 通讯作者: Nakayama

Crystal structure of thymine DNA glycosylase conjugated to SUMO-1

• DOI: 10.1038/nature03634
• 发表时间: 2005-06-16
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Baba, D;Maita, N;Shirakawa, M
• 通讯作者: Shirakawa, M

Structural characterization of MIT domain from human Vps4b..

人类 Vps4b 的 MIT 结构域的结构特征..

• 发表时间: 2005
• 期刊: Biochemical and Biophysical Research Communication 334
• 作者: Takasu;H.;Jee;J.G.;Ohno;A.;Goda;N.;Fujiwara;K.;Tochio;H.;Shirakawa;M.;Hiroaki;H.
• 通讯作者: H.

Structural characterization of the MIT domain from human Vps4b

• DOI: 10.1016/j.bbrc.2005.06.110
• 发表时间: 2005-08-26
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Takasu, H;Jee, JG;Hiroaki, H
• 通讯作者: Hiroaki, H