Regulation of ATP hydrolysis by caldesmon. A novel change in the interaction of myosin with actin.
Regulation of ATP hydrolysis by caldesmon. A novel change in the interaction of myosin with actin.
复制标题
caldesmon 对 ATP 水解的调节。
DOI：
10.1111/j.1749-6632.1990.tb42367.x
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发表时间：
1990
影响因子：
5.2
通讯作者：
Velaz,L
中科院分区：
文献类型：
--
作者：
Chalovich,JM;Hemric,ME;Velaz,L
Caldesmon是一种肌动蛋白和钙调素结合蛋白，它首先从肌胃中分离出来，并显示出抑制平滑肌肌动球蛋白的超沉淀，与主动脉肌中发现的舒张因子相同。2 Caldesmon抑制肌动蛋白激活的smooth ~（3+）和skeletal ~（3+）肌球蛋白及其亚片段ATP水解。钙调素被排除在平滑肌的中间肌动蛋白结构域之外，但存在于收缩性肌动球蛋白结构域中。“在其他细胞中，caldesmon具有与原肌球蛋白相同的分布。最近，钙调素被牵连在受体cappingi 3。14并且已经显示出抑制脱敏的骨骼肌纤维和平滑肌纤维的收缩。由于这些原因以及其他有待讨论的原因，钙调蛋白很可能是平滑肌细胞和非肌肉细胞收缩的调节装置的一个组成部分。我们对caldesmon的兴趣源于这样一个事实，即与肌钙蛋白-原肌球蛋白一样，它是一种肌动蛋白连接的ATP水解调节蛋白。我们感兴趣的是肌动蛋白结合蛋白调节收缩的机制，特别是如果在所有情况下调节都是通过相同的机制发生的，钙调蛋白是肌动蛋白激活的肌球蛋白ATP水解的有效抑制剂，如图1所示。Caldesmon将ATP水解速率降低至单独存在肌动蛋白原肌球蛋白时的速率的约5%。将速率标准化，以比较各种光滑和骨骼肌球蛋白亚片段。钙调素对肌动蛋白激活的ATP酶活性的影响对于骨骼肌球蛋白（未显示）、重质裂肌球蛋白（HMM）和肌球蛋白亚片段1（SI）以及光滑HMM和S-1几乎相同。相反，肌动蛋白激活的ATP酶活性的抑制，钙调蛋白没有影响的基础速率的ATP水解在肌动蛋白的情况下。图2显示了在没有肌动蛋白的情况下，钙调蛋白对光滑肌球蛋白和骨骼肌球蛋白及其亚片段的ATP水解速率的影响。所有肌球蛋白种类的ATP水解的基础速率甚至在4pM钙调素下也不受影响（相当于图1中钙调素比率为0.08）。然而，如图1所示，在50 pM肌动蛋白的存在下，相同浓度的钙调素实际上产生最大抑制。在平滑肌肌球蛋白的情况下，
Caldesmon, an actin-and calmodulin-binding protein that was first isolated from gizzard muscle and shown to inhibit superprecipitation of smooth muscle actomyosin,'is identical with the relaxing factor found in aorta muscle. 2 Caldesmon inhibits the actin-activated ATP hydrolysis of smooth3" and skeletal m~ scle~~ myosins and their subfragments. Caldesmon is excluded from the intermediate filament-actin domain of smooth musclesI0 but is present in the contractile actomyosin domain." In other cells, caldesmon has the same distribution as tropomyosin. I2 Recently, caldesmon has been implicated in receptor cappingi3. 14 and has been shown to inhibit contraction of desensitized skeletal muscle fibersI5 and smooth muscle fibers. I6 For these, and other reasons to be discussed, it is likely that caldesmon is a component of the regulatory apparatus of contraction of smooth and nonmuscle cells. Our interest in caldesmon stems from the fact that, like troponin-tropomyosin, it is an actin-linked regulatory protein of ATP hydrolysis. We are interested in the mechanism of regulation of contraction by actinbinding proteins and in particular if regulation occurs by the same mechanism in all cases.That caldesmon is a potent inhibitor of actin-activated ATP hydrolysis of myosin is shown in FIGURE 1. Caldesmon reduces the rate of ATP hydrolysis to about 5% of the rate in the presence of actin-tropomyosin alone. The rates are normalized to allow comparison of various smooth and skeletal myosin subfragments. The effect of caldesmon on the actin-activated ATPase activity is virtually the same for skeletal myosin (not shown), heavy meromyosin (HMM), and myosin subfragment 1 (SI) as well as smooth HMM and S-1. In contrast to the inhibition of actin-activated ATPase activity, caldesmon has no effect on the basal rate of ATP hydrolysis in the absence of actin. FIGURE 2 shows the effect of caldesmon on the rate of ATP hydrolysis of smooth and skeletal myosin and their subfragments in the absence of actin. The basal rates of ATP hydrolysis of all myosin species were unaffected even at 4 pM caldesmon (equivalent to a caldesmodactin ratio of 0.08 in FIG. 1). This same concentration of caldesmon, however, gave virtually maximum inhibition in the presence of 50 pM actin as shown in FIGURE 1. In the case of smooth muscle myosin the caldesmon concentration