Structural basis of substrate recognition and regulation by ADAM/ADAMTS family proteinases

Research Project

Project/Area Number	26440040
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Structural biochemistry
Research Institution	National Cardiovascular Center Research Institute
Principal Investigator	TAKEDA Soichi 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (80332279)
Project Period (FY)	2014-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	プロテアーゼ / タンパク質間相互作用 / マルチドメイン構造 / 細胞間シグナリング / 基質認識機構 / X線結晶構造解析 / マルチドメイン / 複合体 / モジュラータンパク / 基質認識 / 活性制御 / 前駆体 / 構造生物学 / 蛋白質複合体
Outline of Final Research Achievements	ADAM and ADMTS family of proteins are extracellular modular metalloproteinases composing of several functional domains other than the catalytic domain. ADAM/ADAMTS proteinases play key roles in development and morphogenesis, and are also involved in numerous disease conditions. Most ADAMs are type I membrane proteins whereas all ADAMTS members are soluble proteinases. ADAMs and ADAMTSs share functional domains other than the catalytic domain. The purpose of this study is to elucidate structure-function relationships of ADAM/ADAMTS family proteinases. We have solved crystal structures of the zymogen form of VAP2, a snake venom ADAM, and revealed the common architecture of the pro-domain of ADAM/ADAMTS family proteinases.