Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain
Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain
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DOI：
10.1074/jbc.272.29.18216
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发表时间：
1997-07-18
影响因子：
4.8
通讯作者：
Sykes, BD
中科院分区：
文献类型：
--
作者：
Sia, SK;Li, MX;Sykes, BD
心肌收缩的调节必须与骨骼肌不同，才能产生不同的生理和收缩特性。心肌肌钙蛋白C(TNC)是心肌收缩的关键调节因子，具有不同于骨骼肌肌钙蛋白C的功能和钙结合特性，其钙结合位点I是天然不活跃的。与所有预测的模型和骨骼TNC中观察到的钙诱导结构不同，即使在钙结合(ON)状态下，调节结构域也以一种“封闭”的构象存在，这种处于钙结合状态的结构及其随后与肌钙蛋白I(TnI)的相互作用，对于确定心肌收缩的特定调节机制是至关重要的；这将有助于理解钙增敏药物的作用，这些药物与心脏TNC结合，已知可以增强心脏TNC激活心肌收缩的能力。
The regulation of cardiac muscle contraction must differ from that of skeletal muscles to effect different physiological and contractile properties. Cardiac troponin C (TnC), the key regulator of cardiac muscle contraction, possesses different functional and Ca2+-binding properties compared with skeletal TnC and features a Ca2+-binding site I, which is naturally inactive, The structure of cardiac TnC in the Ca2+-saturated state has been determined by nuclear magnetic resonance spectroscopy. The regulatory domain exists ill a ''closed'' conformation even in the Ca2+-bound (the ''on'') state, in contrast to all predicted models and differing significantly from the calcium-induced structure observed in skeletal TnC, This structure in the Ca2+-bound state, and its subsequent interaction with troponin I (TnI), are crucial in determining the specific regulatory mechanism for cardiac muscle contraction, Further; it will allow for an understanding of the action of calcium-sensitizing drugs, which bind to cardiac TnC and are known to enhance the ability of cardiac TnC to activate cardiac muscle contraction.