STRUCTURAL INVESTIGATIONS OF CALMODULIN COMPLEXES

钙调蛋白复合物的结构研究

• 批准号: 6013679
• 负责人: JAMES K KRANZ
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6013679
• 关键词: binding proteins; calcium ion; calmodulin; myosins; nerve /myelin protein; nuclear magnetic resonance spectroscopy; protein binding; protein protein interaction; protein structure; solutions; structural biology; thermodynamics

The mechanism of protein: protein association will be investigated using the interaction of calmodulin (CaM) and several of its target proteins as a model system. Three dimensional solution structures of CaM bound to various proteins will be determined: 1) the interaction between CaM and peptides corresponding to the two consecutive binding sites in myr4 (myosin I from rat); and 2) the interaction between apoCaM and the whole neuronal protein, neurogranin. The first project will include a thermodynamic investigation of myr4 recognition by CaM, to understand the unusual Ca2+-dependence of the interaction. The CaM:neurogranin structure would represent the first complex of CaM bound to an entire protein. Additional pressure dependence studies will be used to further elucidate the mechanism of this Ca2+-independent interaction, and will require the use of a novel high pressure NMR techniques developed by the Wand group. If time allows, additional thermodynamic studies are proposed addressing the determinants of target recognition using chimeric peptide substrates.

以钙调蛋白（calmodulin, CaM）与几种靶蛋白的相互作用为模型系统，研究蛋白与蛋白的结合机制。CaM与多种蛋白质结合的三维溶液结构将被确定：1)CaM与myr4 （myosin I）中两个连续结合位点对应的肽之间的相互作用；2) apoam与整个神经元蛋白（神经粒蛋白）的相互作用。第一个项目将包括CaM对myr4识别的热力学研究，以了解相互作用中不寻常的Ca2+依赖性。CaM：神经颗粒结构将代表第一个与整个蛋白质结合的CaM复合物。额外的压力依赖性研究将用于进一步阐明这种Ca2+独立相互作用的机制，并将需要使用Wand小组开发的新型高压核磁共振技术。如果时间允许，额外的热力学研究提出解决使用嵌合肽底物的目标识别的决定因素。