Cardiac muscle thin filament structures reveal calcium regulatory mechanism
Cardiac muscle thin filament structures reveal calcium regulatory mechanism
复制标题
DOI：
10.1038/s41467-019-14008-1
复制
发表时间：
2020-01-09
影响因子：
16.6
通讯作者：
Fujii, Takashi
中科院分区：
文献类型：
--
作者：
Yamada, Yurika;Namba, Keiichi;Fujii, Takashi
横纹肌的收缩是由从粗肌丝伸出的肌球蛋白头与肌动蛋白丝的周期性相互作用驱动的，并由肌浆网释放的Ca 2+调节。肌细丝由肌动蛋白、原肌球蛋白和肌钙蛋白组成，Ca 2+与肌钙蛋白结合引发肌钙蛋白和原肌球蛋白构象变化，从而允许肌动蛋白-肌球蛋白相互作用。然而，这种调节机制所涉及的结构变化仍然未知。本文报道了用冷冻电镜观察人心肌细肌丝在Ca ~（2+）存在和不存在时的结构。基于现有晶体结构建立的两种状态的分子模型揭示了肌钙蛋白I的C-末端区域和肌钙蛋白T的N-末端区域的结构，其与原肌球蛋白的头-尾连接以及肌动蛋白丝上的肌钙蛋白核心复合。细纤维的Ca 2+结合后的结构变化现在揭示了Ca 2+调节肌肉收缩的机制。
Contraction of striated muscles is driven by cyclic interactions of myosin head projecting from the thick filament with actin filament and is regulated by Ca2+ released from sarcoplasmic reticulum. Muscle thin filament consists of actin, tropomyosin and troponin, and Ca2+ binding to troponin triggers conformational changes of troponin and tropomyosin to allow actin-myosin interactions. However, the structural changes involved in this regulatory mechanism remain unknown. Here we report the structures of human cardiac muscle thin filament in the absence and presence of Ca2+ by electron cryomicroscopy. Molecular models in the two states built based on available crystal structures reveal the structures of a C-terminal region of troponin I and an N-terminal region of troponin T in complex with the head-to-tail junction of tropomyosin together with the troponin core on actin filament. Structural changes of the thin filament upon Ca2+ binding now reveal the mechanism of Ca2+ regulation of muscle contraction.