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)用小角X射线散射（SAXS）研究了钙调素与肌球蛋白轻链激酶、钙调磷酸酶、钙调蛋白蛋白-蛋白激酶中钙调素结合序列结合后的构象变化。一，二，9 -2）SAXS用于研究钙调蛋白与神经元特异性蛋白CAP-23/NAP-22的豆蔻酰化N-末端九肽结合时的构象变化，并在分子水平上确定结合基序。9 -3）SAXS用于研究钙调蛋白与拮抗剂如W-7和TFP，并在分子水平上确定结合基序。9 -4）在不存在Ca^<2+>的情况下，在钙调素/TFP和钙调素/钙调素依赖性蛋白激酶TV复合物中发现了一个新的结合基序。9 -5）小角X射线散射用于揭示钙调素中中心螺旋的作用，以使其消失。9 -6）小角X射线散射具有终止的-利用流动技术研究了钙调蛋白识别Ca^2+依赖性靶分子的动力学构象变化。

项目成果

和泉 義信: "アタクチックポリスチレン物理ゲルの構造と機構" 高分子論文集. 55・12. 749-759 (1998)

泉义伸：“无规聚苯乙烯物理凝胶的结构和机理”《高分子科学与技术》杂志55・12（1998）。

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。

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

N.Matsushima，N.hayachi，Y.Jinbo.Y-lzumi：“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 (2000