Elucidation of structural mechanism of substrate selection and secretion signal in T3SS secretion by theoretical and experimental structural biology

通过理论和实验结构生物学阐明T3SS分泌中底物选择和分泌信号的结构机制

• 批准号: 24790411
• 负责人: SATO Yoshiharu
• 金额: $ 2.91万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790411/
• 关键词: サルモネラ; III型分泌装置; エフェクター; 病原因子; バイオインフォマティクス; III型分泌機構; 国際情報交換; カナダ

Many bacterial pathogens manipulate cellular functions of host cells by injecting virulence proteins(T3SS effectors) into host cells using T3SS apparatus. Structural modeling analysis and biochemical experiments revealed that substrate selection and the recognition in T3SS secretion are conducted by the similar mechanism as used in the system of AAA+ protease ClpXP-substrate interaction. Based on the findings, structural property analysis was integrated into the effector prediction system, and the prediction accuracy was further improved. Experimental validation for 9 putative Salmonella effectors listed by this program revealed that five novel effectors including STM1239 were confirmed to secrete into supernatant of culture media.

许多细菌病原体通过使用T3SS装置将毒力蛋白(T3SS效应物)注射到宿主细胞中来操纵宿主细胞的细胞功能。结构模型分析和生化实验表明，T3SS分泌中底物的选择和识别的机制与AAA+蛋白酶ClpXP-底物相互作用的机制相似。在此基础上，将结构特性分析融入到效应器预测系统中，进一步提高了预测精度。对该程序列出的9个可能的沙门氏菌效应物的实验验证表明，包括STM1239在内的5个新的效应物被证实分泌到培养上清液中。

项目成果

Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of Theileria-induced leukocyte transformation.

• DOI: 10.1128/mbio.00204-12
• 发表时间: 2012
• 期刊: mBio
• 影响因子: 6.4
• 作者: Hayashida K;Hara Y;Abe T;Yamasaki C;Toyoda A;Kosuge T;Suzuki Y;Sato Y;Kawashima S;Katayama T;Wakaguri H;Inoue N;Homma K;Tada-Umezaki M;Yagi Y;Fujii Y;Habara T;Kanehisa M;Watanabe H;Ito K;Gojobori T;Sugawara H;Imanishi T;Weir W;Gardner M;Pain A;Shiels B;Hattori M;Nene V;Sugimoto C
• 通讯作者: Sugimoto C

Prediction of protein-destabilizing polymorphisms by manual curation with protein structure.

• DOI: 10.1371/journal.pone.0050445
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gough CA;Homma K;Yamaguchi-Kabata Y;Shimada MK;Chakraborty R;Fujii Y;Iwama H;Minoshima S;Sakamoto S;Sato Y;Suzuki Y;Tada-Umezaki M;Nishikawa K;Imanishi T;Gojobori T
• 通讯作者: Gojobori T

協調的認識により調節されるAAA+プロテアーゼClpXPの基質特異性

协同识别调节 AAA+ 蛋白酶 ClpXP 的底物特异性

• 发表时间: 2013
• 作者: Goto Y;Sanjoba C;Reed SG;Noiri E;Matsumoto Y;佐藤慶治
• 通讯作者: 佐藤慶治

理論計算と生化学研究により明らかにされたAAA+プロテアーゼClpXPによる基質FlhD4C2の協調的認識機構

理论计算和生化研究揭示AAA+蛋白酶ClpXP对底物FlhD4C2的协同识别机制

• 发表时间: 2012
• 作者: 佐藤 慶治;高屋 明子;ワリッド ホーリー;山本 友子
• 通讯作者: 山本 友子

PCDq: human protein complex database with quality index which summarizes different levels of evidences of protein complexes predicted from h-invitational protein-protein interactions integrative dataset.

• DOI: 10.1186/1752-0509-6-s2-s7
• 发表时间: 2012
• 期刊: BMC systems biology
• 作者: Kikugawa S;Nishikata K;Murakami K;Sato Y;Suzuki M;Altaf-Ul-Amin M;Kanaya S;Imanishi T
• 通讯作者: Imanishi T