Project Elad, Friedman Ran, Nachliel Esther, Gutman Menachem
Laser Laboratory for Fast Reactions in Biology Biochemistry, Tel Aviv University, 69978 Tel Aviv, Israel.
Biophys J. 2006 Jun 1;90(11):3842-50. doi: 10.1529/biophysj.105.077792. Epub 2006 Mar 13.
Calmodulin is a small (148 residues), ubiquitous, highly-conserved Ca(2+) binding protein serving as a modulator of many calcium-dependent processes. In this study, we followed, by means of molecular dynamics, the structural stability of the protein when one of its four bound Ca(2+) ions is removed, and compared it to a simulation of the fully Ca(2+) bound protein. We found that the removal of a single Ca(2+) ion from the N-lobe of the protein, which has a lower affinity for the ion, is sufficient to initiate a considerable structural rearrangement. Although the overall structure of the fully 4 Ca(2+) bound protein remained intact in the extended conformation, the Ca(2+)-removed protein changed its conformation into a compact state. The observation that the 3 Ca(2+) loaded protein assumes a compacted solution state is in accord with experimental observation that the NSCP protein, which binds only three Ca(2+) ions, is natively in a compact state. Examination of the folding dynamics reveals a cooperation between the C-lobe, N-lobe, and the interdomain helix that enable the conformation change. The forces driving this conformational change are discussed.
钙调蛋白是一种小蛋白（148个残基），广泛存在且高度保守，是一种钙结合蛋白，可作为许多钙依赖性过程的调节剂。在本研究中，我们通过分子动力学方法，研究了该蛋白四个结合钙离子中的一个被去除时的结构稳定性，并将其与完全结合钙离子的蛋白模拟结果进行了比较。我们发现，从对钙离子亲和力较低的蛋白N叶中去除单个钙离子，足以引发相当大的结构重排。尽管完全结合4个钙离子的蛋白的整体结构在伸展构象中保持完整，但去除钙离子后的蛋白将其构象转变为紧凑状态。加载3个钙离子的蛋白呈现紧凑溶液状态的观察结果与实验观察一致，即仅结合3个钙离子的NSCP蛋白天然处于紧凑状态。对折叠动力学的研究揭示了C叶、N叶和结构域间螺旋之间的协同作用，这使得构象发生变化。讨论了驱动这种构象变化的力。
