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（小泛素样修饰剂）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，例如转录、DNA 修复和染色质结构调节。靶蛋白之一胸腺嘧啶 DNA 糖基化酶 (TDG) 是一种 DNA 糖基化酶，被认为可以从含有 G-U 或 G-T 碱基对的 DNA 中切除不匹配的碱基。 TDG 的 SUMO-1 或 SUMO-2/3 附着被提议促进其与含有脱碱基位点的 DNA 解离。我们已经确定了 TDG 中心区域的晶体结构，其中涉及催化核心结构域和 SUMO 化位点，与 SUMO-1 (SUMO-1-TDG) 或 SUMO-3 (SUMO-3-TDG) 缀合。 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。模型构建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出物，该突出物的位置是为了与与 TDG 结合的 DNA 产生空间冲突。 SUMO-3-TDG的结构与SUMO-1-TDG相似。

项目成果

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

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.

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.

Structure of the N-terminal domain of PEX1 AAA-ATPase : characterization of a putative adaptor-binding domain.

PEX1 AAA-ATPase N 端结构域的结构：假定的接头结合域的表征。

• 发表时间: 2004
• 期刊: Journal of Biological Chemistry 279
• 作者: Shiozawa;K.;Maita;N.;Tomii;K.;Seto;A.;Goda N.;Akiyama;Y.;Shimizu;T.;Shirakawa;M.;Hiroaki;H.
• 通讯作者: H.

Small ubiquitiirlike modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9.

Ad4 结合蛋白/类固醇生成因子 1 (Ad4BP/SF-1) 协同控制基序的小泛素样修饰符 1 (SUMO-1) 修饰调节 Ad4BP/SF-1 和 Sox9 之间的协同转录。

• 发表时间: 2004
• 期刊: Molecular Endocrinology 18
• 作者: Komatsu;T.;Mizusaki;H.;Mukai;T.;Ogawa;H.;Baba;D.;Shirakawa. M.. Hatakeyama;S.;Nakayama;K. I.;Yamamoto;H.;Kikuchi;A.;Morohashi;K.
• 通讯作者: K.