Takeda Soichi, Yamashita Atsuko, Maeda Kayo, Maéda Yuichiro
Laboratory for Structural Biochemistry, RIKEN Harima Institute at SPring-8, Mikazuki, Sayo, Hyogo, Japan.
Nature. 2003 Jul 3;424(6944):35-41. doi: 10.1038/nature01780.
Troponin is essential in Ca(2+) regulation of skeletal and cardiac muscle contraction. It consists of three subunits (TnT, TnC and TnI) and, together with tropomyosin, is located on the actin filament. Here we present crystal structures of the core domains (relative molecular mass of 46,000 and 52,000) of human cardiac troponin in the Ca(2+)-saturated form. Analysis of the four-molecule structures reveals that the core domain is further divided into structurally distinct subdomains that are connected by flexible linkers, making the entire molecule highly flexible. The alpha-helical coiled-coil formed between TnT and TnI is integrated in a rigid and asymmetric structure (about 80 angstrom long), the IT arm, which bridges putative tropomyosin-anchoring regions. The structures of the troponin ternary complex imply that Ca(2+) binding to the regulatory site of TnC removes the carboxy-terminal portion of TnI from actin, thereby altering the mobility and/or flexibility of troponin and tropomyosin on the actin filament.
肌钙蛋白在钙离子对骨骼肌和心肌收缩的调节中至关重要。它由三个亚基（肌钙蛋白T、肌钙蛋白C和肌钙蛋白I）组成，并与原肌球蛋白一起位于肌动蛋白丝上。在此，我们展示了处于钙离子饱和形式的人心脏肌钙蛋白核心结构域（相对分子质量分别为46,000和52,000）的晶体结构。对四分子结构的分析表明，核心结构域进一步分为由柔性连接子相连的结构不同的亚结构域，这使得整个分子具有高度的柔性。在肌钙蛋白T和肌钙蛋白I之间形成的α-螺旋卷曲螺旋整合在一个刚性且不对称的结构（约80埃长）中，即IT臂，它连接假定的原肌球蛋白锚定区域。肌钙蛋白三元复合物的结构表明，钙离子与肌钙蛋白C的调节位点结合会使肌钙蛋白I的羧基末端部分从肌动蛋白上移除，从而改变肌钙蛋白和原肌球蛋白在肌动蛋白丝上的移动性和/或柔性。
