STRUCTURAL INVESTIGATIONS OF CALMODULIN COMPLEXES

蛋白质的作用机制：将使用钙调素（CaM）和其几种靶蛋白的相互作用作为模型系统来研究蛋白质缔合。 将确定与各种蛋白质结合的CaM的三维溶液结构：1）CaM与对应于myr 4（来自大鼠的肌球蛋白I）中的两个连续结合位点的肽之间的相互作用;和2）apoCaM与整个神经元蛋白质，神经颗粒蛋白之间的相互作用。 第一个项目将包括由CaM识别myr 4的热力学研究，以了解相互作用的不寻常的Ca 2+依赖性。钙调素：神经颗粒蛋白结构将代表钙调素结合到整个蛋白质的第一个复合物。 额外的压力依赖性的研究将用于进一步阐明这种Ca 2+独立的相互作用的机制，并将需要使用一种新的高压NMR技术开发的Wand组。 如果时间允许，提出了额外的热力学研究，解决目标识别的决定因素，使用嵌合肽底物。

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.