Robinson John M, Dong Wen-Ji, Xing Jun, Cheung Herbert C
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-2041, USA.
J Mol Biol. 2004 Jul 2;340(2):295-305. doi: 10.1016/j.jmb.2004.04.046.
The principal task of the Ca(2+) activation of striated muscle is the release of the troponin I (TnI) inhibitory region (TnI-I) from actin. TnI-I release facilitates the repositioning of tropomyosin across the actin surface and the formation of strong, force generating, actin-myosin cross-bridges. Full activation of the Ca(2+) regulatory switch (CRS) requires two switching steps in cTnI: binding of the TnI regulatory region to hydrophobic sites in the N-domain of Ca(2+)-bound troponin C and release of the adjacent TnI-I from actin. Using Förster resonance energy transfer, we have examined the requirements for full activation of the cardiac CRS. In the presence of actin, both Ca(2+) and strong cross-bridges are required for full activation. Actin desensitizes the CRS to Ca(2+) and produces cooperativity in the Ca(2+) activation of the CRS. Strong cross-bridges eliminate cooperativity and re-sensitize the CRS to Ca(2+). We propose a kinetic scheme and a structural model to account for these findings.
横纹肌钙（Ca²⁺）激活的主要任务是从肌动蛋白上释放肌钙蛋白I（TnI）抑制区（TnI-I）。TnI-I的释放有助于原肌球蛋白在肌动蛋白表面重新定位，并形成强大的、产生力的肌动蛋白-肌球蛋白横桥。Ca²⁺调节开关（CRS）的完全激活在肌钙蛋白I（cTnI）中需要两个转换步骤：TnI调节区与结合Ca²⁺的肌钙蛋白C的N结构域中的疏水位点结合，以及相邻的TnI-I从肌动蛋白上释放。利用福斯特共振能量转移，我们研究了心脏CRS完全激活的条件。在有肌动蛋白存在的情况下，完全激活需要Ca²⁺和强大的横桥。肌动蛋白使CRS对Ca²⁺脱敏，并在CRS的Ca²⁺激活中产生协同性。强大的横桥消除协同性，并使CRS对Ca²⁺重新敏感。我们提出了一个动力学方案和一个结构模型来解释这些发现。
