Molecular Mechanism of Target Recognition by Calmodulin

钙调蛋白识别靶点的分子机制

• 批准号: 10450358
• 负责人: IZUMI Yoshinobu
• 金额: $ 9.02万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10450358/
• 关键词: Calmodulin; Myosin light chain kinase; Calcineurin; Calmodulin-dependent protein kinase I, II, IV; CAP-23; NAP-22; W-7; TFP; Recognition Sequence; 標準的標的分子; 非標準的標的分子; カルモデュリン依存性プロテインキナーゼ; アポカルモデュリン; NAPIZZ; 標的ペプチド; 分子認識モチーフ; 放射光小角散乱; 多機能性発

9-1) Small-angle X-ray scattering (SAXS) was used to investigate the conformational changes of calmodulin on binding to a calmodulin-binding sequence in myosin light chain kinase, calcineurin, calmodulin-protein kinase. I, II, IV and these binding motifs were determined on the molecular level.9-2) SAXS was used to investigate the conformational changes of calmodulin on binding to a myristoylated N-terminal nonapeptide from neuron-specific protein CAP-23/NAP-22 and the binding motif was determined on the molecular level.9-3) SAXS was used to investigate the conformational changes of calmodulin on binding to an antagonist like W-7 and TFP and the binding motif was determined on the molecular level.9-4) In the absence of Ca^<2+>, a new binding motif was found in the calmodulin/TFP and calmodulin/calmodulin-dependent protein kinase TV complexes.9-5) SAXS was used to reveal the role of the central helix in calmodulin for its recognition.9-6) SAXS with stopped-flow technique was used to reveal the kinetic conformational change of Ca^<2+>-dependent target recognition by calmodulin.

9-1）小角度X射线散射（SAXS）用于研究钙调蛋白与肌球蛋白光链激酶，钙调蛋白，钙调蛋白 - 蛋白激酶结合结合与钙调蛋白结合序列的构象变化。 I，II，IV和这些结合基序是在分子水平上确定的。9-2）SAXS用于研究钙调蛋白在结合与肉豆蔻酰胺的N端非肽结合的构象变化中，从神经元特异性蛋白质蛋白Cap-23/nap-22中确定了与分子的结合，并确定了与分子的结合。在分子水平上确定了像W-7和TFP和结合基序的拮抗剂。9-4）在没有CA^<2+>的情况下，在钙调蛋白/TFP和钙调蛋白/钙调蛋白/钙调蛋白依赖性蛋白依赖性蛋白激酶的蛋白质激酶电视中发现了一个新的sax-saxs saxs saxs inix for sax inix for sax inix for sax inix in Callix inix for sax inix inix for nix of Calmins of Calmod of Calmin of Calmin inix in Calmif中，发现了一个新的结合基序。使用停止流动的技术，用于揭示CA^<2+> - 依赖性靶标的钙抑制蛋白的动力构象变化。

项目成果

M.Osawa, S.Kuwamoto, Y.Izumi 他: "Evidence for calmodulin inter-domain compaction in solusion induced by W-7 binding" FEBs Lett.442. 173-177 (1999)

M.Osawa、S.Kuwamoto、Y.Izumi 等人：“W-7 结合诱导的溶液中钙调蛋白域间压缩的证据”FEBs Lett.442 (1999)。

Y.Izumi, H.Takezawa, N.Kikuta, S.Uemura, A.Tsutsumi: "Two-Stage Melting in Dilute Gels of poly (g-benzyl L-glutamate)"Macromlecules. 31. 430-435 (1998)

Y.Izumi、H.Takezawa、N.Kikuta、S.Uemura、A.Tsutsumi：“聚（g-苄基L-谷氨酸）稀凝胶中的两阶段熔化”大分子。

Y.Izumi, S.Saito, K.Sowa: "DSC and structural studie ofset-gel transition of gellan sum in water" Prog.Coll.Polym.Sci.印刷中. (1999)

Y.Izumi、S.Saito、K.Sowa：“结冷胶在水中的凝固凝胶转变的结构研究”Prog.Coll.Polym.Sci 出版中。

M.Osawa, S.Kuwamoto, Y.Izumi, K.L.Yorp, M.Ikura, N.Matsusima: "Evidenae for calmodulin inter-dowain compaition in solution"FEBS Letters. 442. 173-177 (1999)

M.Osawa、S.Kuwamoto、Y.Izumi、K.L.Yorp、M.Ikura、N.Matsusima：“溶液中钙调蛋白域间竞争的证据”FEBS 快报。

N.Matsushima, N.Hayasi, Y.Jinbo, Y.Izumi.: "Ca^<2+>-bound calmodulin forms a compact globular structure on binding four trifluoperazine molecules in solution"Biochem.J.. 347. 211-215 (2000)

N.Matsushima、N.Hayasi、Y.Jinbo、Y.Izumi.：“Ca^2-结合的钙调蛋白在溶液中结合四个三氟拉嗪分子时形成致密的球状结构”Biochem.J.. 347. 211-215 (