Lehrer S S, Geeves M A
Muscle Research Group, Boston Biomedical Research Institute, Boston, MA 01224, USA.
J Mol Biol. 1998 Apr 17;277(5):1081-9. doi: 10.1006/jmbi.1998.1654.
It is generally accepted that the regulation of muscle contraction involves cooperative and allosteric interactions among the protein components, actin, myosin, tropomyosin and troponin. But, as yet, the individual role of each component has not been clearly identified. Here we compare the properties of the components of the muscle regulatory system with the corresponding components of two systems, hemoglobin and aspartate transcarbamylase, that are well described by the classical Monod, Wyman and Changeux (MWC) model. The analogy indicates that actin is the catalytic subunit, tropomyosin is the regulatory subunit and troponin in the absence and presence of Ca2+ is the allosteric inhibitor and activator, respectively. The analogy additionally indicates that the substrate is myosin-ATP (or myosin-ADP-Pi) rather than ATP. Also, in contrast to other MWC systems, the activating ligand for actin-tropomyosin is a myosin-nucleotide intermediate or product that binds tightly to actin, rather than the substrate which binds weakly. This tightly bound intermediate switches the system from the off-state to the on-state (T to R-state in MWC nomenclature) in a concerted transition, affecting n actin subunits, allowing force to be developed.
人们普遍认为，肌肉收缩的调节涉及肌动蛋白、肌球蛋白、原肌球蛋白和肌钙蛋白等蛋白质成分之间的协同和变构相互作用。但是，到目前为止，每个成分的具体作用尚未明确确定。在这里，我们将肌肉调节系统的成分特性与血红蛋白和天冬氨酸转氨甲酰酶这两个系统的相应成分进行比较，这两个系统已被经典的莫诺、怀曼和尚热（MWC）模型很好地描述。这种类比表明，肌动蛋白是催化亚基，原肌球蛋白是调节亚基，在不存在和存在Ca2+的情况下，肌钙蛋白分别是变构抑制剂和激活剂。这种类比还表明，底物是肌球蛋白-ATP（或肌球蛋白-ADP-磷酸）而不是ATP。此外，与其他MWC系统不同，肌动蛋白-原肌球蛋白的激活配体是一种与肌动蛋白紧密结合的肌球蛋白-核苷酸中间体或产物，而不是与肌动蛋白弱结合的底物。这种紧密结合的中间体以协同转变的方式将系统从关闭状态切换到开启状态（在MWC命名法中从T态转变为R态），影响n个肌动蛋白亚基，从而使肌肉能够产生力量。
