Electrostatic control of the overall shape of calmodulin: numerical calculations
Electrostatic control of the overall shape of calmodulin: numerical calculations
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DOI：
10.1007/s00249-006-0123-1
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发表时间：
2007-03-01
影响因子：
2
通讯作者：
Alexov, E.
中科院分区：
文献类型：
--
作者：
Isvoran, A.;Craescu, C. T.;Alexov, E.
该论文报告了可电离基团的 pKa 的数值计算结果以及钙调蛋白三种不同状态下钙调蛋白叶之间静电相互作用的结果：无钙、无肽；含钙，不含肽；以及钙负载、肽结合。 NMR 和 X 射线研究表明，在这些状态下，钙调蛋白的整体结构采用各种构象，分别称为：无序半紧凑构象、延伸构象和紧凑构象。此外，最近报道的一种新的X射线结构(Structure, 2003, 11, 1303)表明，除了众所周知的延伸构象外，负载钙的、无肽的钙调蛋白还可以采用紧凑的构象。计算出的载钙、无肽钙调蛋白沿着连接这两种构象的路径的能量变化为这种结构可塑性提供了可能的解释。因此，溶液相中的 pH 值和有机化合物对钙调蛋白选择紧凑或延伸构象的影响可能是合理的。电离变化对钙调蛋白叶缔合能的贡献的分析表明，致密形式的形成需要几个酸性残基的质子化。然而，揭示了两种不同的质子化情况：由于内部叶组织导致的质子化，因此独立于叶关联，以及由叶关联引起的质子化导致质子摄取。此外，在两种紧凑构象（无肽和肽结合）中计算了单个残基对钙调蛋白叶结合能的作用，并表明一组残基始终在域间相互作用中发挥主导作用。
The paper reports the results of numerical calculations of the pKa's of the ionizable groups and the electrostatic interactions between calmodulin lobes in three different states of calmodulin: calcium-free, peptide-free; calcium-loaded, peptide-free; and calcium-loaded, peptide-bound. NMR and X-ray studies revealed that in these states the overall structure of calmodulin adopts various conformations referred as: disordered semi-compact, extended and compact conformations, respectively. In addition, a new X-ray structure was recently reported (Structure, 2003, 11, 1303) showing that calcium-loaded, peptide-free calmodulin can also adopt a compact conformation in addition to the well known extended conformation. The calculated energy changes of calcium-loaded, peptide-free calmodulin along the pathway connecting these two conformations provide a possible explanation for this structural plasticity. The effect of pH and organic compounds in the solution phase on the preference of calmodulin to adopt compact or extended conformations may be thus rationalized. Analysis of the contribution of the ionization changes to the energy of association of calmodulin lobes suggested that the formation of the compact forms requires protonation of several acidic residues. However, two different protonation scenarios are revealed: a protonation due to internal lobe organization and thus independent of the lobes association, and a protonation induced by the lobes association resulting to a proton uptake. In addition, the role of the individual residues on the energy of association of calmodulin lobes is calculated in two compact conformations (peptide-free and peptide-bound) and is shown that a set of residues always plays a dominant role in inter-domain interactions.