Babu A, Gulati J
Albert Einstein College of Medicine, Department of Medicine and Physiology/Biophysics, Bronx, NY 10461.
Biochem Biophys Res Commun. 1990 Feb 14;166(3):1421-8. doi: 10.1016/0006-291x(90)91025-n.
To gain insights into the mechanism of the central helix of calmodulin and troponin-C in the Ca2(+)-regulation of force development in striated and smooth muscles, the present study was made of the TFP induced inhibition of contraction, and of the uptake of these proteins by skinned fibers. Calmodulin was four-fold more sensitive to TFP than TnC, but the inhibition was found to be identical for skeletal and cardiac muscles despite the differences in their troponin-C isoforms. Also, the results were comparable between fast-twitch fiber, when calmodulin was exchanged for troponin-C to act on TnI, and smooth muscle, where calmodulin acts on myosin light chain kinase. These findings indicate that the inhibition of force by TFP is entirely due to its binding to the hydrophobic sites in the central helix. The uptakes of troponin-C and calmodulin were also different, and this is explained by a TFP-independent domain in troponin-C that binds TnI.
为深入了解钙调蛋白和肌钙蛋白C的中央螺旋在横纹肌和平滑肌Ca2+调节力发展中的作用机制，本研究对三氟拉嗪（TFP）诱导的收缩抑制以及这些蛋白质被去垢剂处理的肌纤维摄取情况进行了研究。钙调蛋白对TFP的敏感性是肌钙蛋白C的四倍，但尽管骨骼肌和心肌的肌钙蛋白C同工型存在差异，发现对它们的抑制作用是相同的。此外，当用钙调蛋白替换肌钙蛋白C作用于肌钙蛋白I时，快肌纤维与钙调蛋白作用于肌球蛋白轻链激酶的平滑肌之间的结果具有可比性。这些发现表明，TFP对力的抑制完全是由于其与中央螺旋中的疏水位点结合。肌钙蛋白C和钙调蛋白的摄取也不同，这可以用肌钙蛋白C中一个与肌钙蛋白I结合的不依赖TFP的结构域来解释。
