Cardiac myosin-binding protein C modulates the tuning of the molecular motor in the heart
Cardiac myosin-binding protein C modulates the tuning of the molecular motor in the heart
复制标题
DOI：
10.1529/biophysj.107.127787
复制
发表时间：
2008-07-15
影响因子：
3.4
通讯作者：
Coirault, Catherine
中科院分区：
文献类型：
--
作者：
Lecarpentier, Yves;Vignier, Nicolas;Coirault, Catherine
心肌肌球蛋白结合蛋白C（cMyBP-C）是心肌收缩力的重要调节因子。其对肌球蛋白跨桥（CB）的确切作用尚不清楚。使用cMyBP-C-/-小鼠模型，我们确定了cMyBP-C如何调节CB与肌动蛋白的循环相互作用。根据乳头肌力学，使用A. F.赫胥黎方程肌球蛋白与肌动蛋白弱结合的概率在cMyBP-C-/-中比在cMyBP-C+/+中高。然而，在cMyBP-C-/-中，处于强结合、高力产生状态的CB数量和每个CB产生的力较低。在cMyBP-C-/-中，总体CB循环和CB倾斜速度加快。利用cMyBP-C+/-肌球蛋白溶液中存在cMyBP-C而非cMyBP-C-/-的优势，我们还分析了cMyBP-C对肌动蛋白基于肌球蛋白的滑动速度的影响。哀叹。在基线处，滑动速度和相对等长CB力，如通过阻止变薄所需的α-辅肌动蛋白的量所确定的。与cMyBP-C +/+相比，cMyBP-C-/-中的小鼠运动性较低。cAMP依赖性蛋白激酶介导的cMyBP-C磷酸化进一步增加了CB产生的力。我们的结论是，cMyBP-C防止低效，弱结合的肌球蛋白CB肌动蛋白，并有一个关键的影响，对动力冲程步骤的肌球蛋白分子马达。
Cardiac myosin binding protein C (cMyBP-C) is an important regulator of cardiac contractility. Its precise effect on myosin cross-bridges (CBs) remains unclear. Using a cMyBP-C-/- mouse model, we determined how cMyBP-C modulates the cyclic interaction of CBs with actin. From papillary muscle mechanics, CB characteristics were provided using A. F. Huxley's equations. The probability of myosin being weakly bound to actin was higher in cMyBP-C-/- than in cMyBP-C+/+. However, the number of CBs in strongly bound, high-force generated state and the force generated per CB were lower in cMyBP-C-/-. Overall CB cycling and the velocity of CB tilting were accelerated in cMyBP-C-/-. Taking advantage of the presence of cMyBP-C in cMyBP-C+/- myosin solution but not in cMyBP-C-/-, we also analyzed the effects of cMyBP-C on the myosin-based sliding velocity of actin. laments. At baseline, sliding velocity and the relative isometric CB force, as determined by the amount of alpha-actinin required to arrest thin. lament motility, were lower in cMyBP-C-/- than in cMyBP-C+/+. cAMP-dependent protein kinase-mediated cMyBP-C phosphorylation further increased the force produced by CBs. We conclude that cMyBP-C prevents inefficient, weak binding of the myosin CB to actin and has a critical effect on the power-stroke step of the myosin molecular motor.