An interaction-based analysis of calcium-induced conformational changes in Ca2+ sensor proteins.
An interaction-based analysis of calcium-induced conformational changes in Ca2+ sensor proteins.
复制标题
对钙诱导的 Ca2 传感器蛋白构象变化进行基于相互作用的分析。
DOI：
10.1002/pro.5560070206
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Chazin,WJ
中科院分区：
文献类型：
--
作者：
Nelson,MR;Chazin,WJ
钙感受器蛋白通过在钙离子结合时发生显著的构象变化，将细胞内钙离子水平的瞬时升高转化为代谢或机械反应。对钙结合诱导的典型钙传感器钙调素(CaM)和肌钙蛋白C的构象变化进行了详细的分析，以深入了解它们对钙结合反应的潜在分子基础。使用距离差矩阵、残基间接触分析、螺旋角比较和使用分子图形检查结构来对各种结构进行无偏见的比较。钙诱导的这些蛋白质的构象变化是由每个结构域内四个螺旋的堆积重组所主导的。对闭合和开放构象的比较证实，钙结合导致每个EF-手中的开放。对CaM(CaM-C)C-端结构域的二次分析清楚地表明，在无钙情况下，CaM-C处于闭合构象，这与肌球蛋白轻链C-末端Ef-Hand结构域中观察到的半开放构象不同。这些研究深入了解了这些变化的结构基础，以及EF-Hand钙结合蛋白家族不同成员对钙结合的不同反应。讨论了影响钙离子开放构象稳定性的因素，包括一个新的假设，即临界疏水相互作用稳定了钙离子传感器中的开放构象，但在与钙离子结合后保持关闭状态的“非传感器”蛋白质中则不存在。甲硫氨酸残基在稳定开放构象中的作用也被提出。
Calcium sensor proteins translate transient increases in intracellular calcium levels into metabolic or mechanical responses, by undergoing dramatic conformational changes upon Ca2+binding. A detailed analysis of the calcium binding‐induced conformational changes in the representative calcium sensors calmodulin (CaM) and troponin C was performed to obtain insights into the underlying molecular basis for their response to the binding of calcium. Distance difference matrices, analysis of interresidue contacts, comparisons of interhelical angles, and inspection of structures using molecular graphics were used to make unbiased comparisons of the various structures. The calcium‐induced conformational changes in these proteins are dominated by reorganization of the packing of the four helices within each domain. Comparison of the closed and open conformations confirms that calcium binding causes openingwithineach of the EF‐hands. A secondary analysis of the conformation of the C‐terminal domin of CaM (CaM‐C) clearly shows that CaM‐C occupies a closed conformation in the absence of calcium that is distinct from the semi‐open conformation observed in the C‐terminal EF‐hand domains of myosin light chains. These studies provide insight into the structural basis for these changes and into the differential response to calcium binding of various members of the EF‐hand calcium‐binding protein family. Factors contributing to the stability of the Ca2+‐loaded open conformation are discussed, including a new hypothesis that critical hydrophobic interactions stabilize the open conformation in Ca2+ sensors, but are absent in “non‐sensor” proteins that remain closed upon Ca2+binding. A role for methionine residues in stabilizing the open conformation is also proposed.