Structure of the core domain of human cardiac troponin in the Ca2+-saturated form
Structure of the core domain of human cardiac troponin in the Ca2+-saturated form
复制标题
DOI：
10.1038/nature01780
复制
发表时间：
2003-07-03
期刊：
影响因子：
64.8
通讯作者：
Maéda, Y
中科院分区：
文献类型：
--
作者：
Takeda, S;Yamashita, A;Maéda, Y
肌钙蛋白在Ca2+调节骨骼肌和心肌收缩中是必不可少的。它由三个亚基（TnT， TnC和TnI）组成，与原肌球蛋白一起位于肌动蛋白丝上。在这里，我们展示了Ca2+饱和形式的人心脏肌钙蛋白的核心结构域（相对分子质量为46,000和52,000）的晶体结构。对四分子结构的分析表明，核心结构域进一步划分为结构不同的子结构域，这些子结构域通过柔性连接体连接，使整个分子具有高度的柔性。在TnT和TnI之间形成的α螺旋螺旋状线圈整合在一个刚性和不对称结构（约80埃长）中，即IT臂，它连接了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，Ca2+结合到TnC的调节位点，将TnI的羧基末端从肌动蛋白上移除，从而改变肌钙蛋白和原肌球蛋白在肌动蛋白丝上的流动性和/或灵活性。
Troponin is essential in Ca2+ 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 Ca2+-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 Ca2+ 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.