STRUCTURAL INVESTIGATIONS OF CALMODULIN COMPLEXES

蛋白质的作用机制：以钙调素(CaM)与其靶蛋白的相互作用为模型系统，研究蛋白质的相互作用。将确定CaM与各种蛋白质结合的三维溶液结构：1)CaM与myr4(大鼠肌球蛋白I)上两个连续结合位点对应的多肽之间的相互作用；2)apoCaM与整个神经元蛋白-神经颗粒素的相互作用。第一个项目将包括CaM识别myr4的热力学研究，以了解相互作用的不寻常的钙依赖。CaM：神经颗粒素结构将代表CaM与整个蛋白质结合的第一个复合体。更多的压力依赖性研究将被用来进一步阐明这种不依赖于钙的相互作用的机制，并将需要使用由Wand小组开发的新的高压核磁共振技术。如果时间允许，建议进行更多的热力学研究，以解决使用嵌合多肽底物识别目标的决定因素。

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.