Advanced ICT Research Institute, National Institute of Information and Communications Technology, Iwaoka 588-2, Iwaoka-cho, Nishi-ku, Kobe 651-2492, Japan.
J Muscle Res Cell Motil. 2013 May;34(2):115-23. doi: 10.1007/s10974-013-9339-8. Epub 2013 Mar 28.
Molluscan muscle twitchin, a titin/connectin-related giant protein, regulates interactions between actin and myosin filaments at low Ca(2+) concentrations. When it is dephosphorylated, actin filaments tightly bind to myosin filaments, resulting in the catch state known as the state of high passive tension with very low energy consumption. Yet when twitchin is phosphorylated actin filaments detach from the myosin filaments, resulting in relaxation of the catch. Here, steady-state Mg-ATPase activities of purified myosin were measured under various conditions: without twitchin, with dephosphorylated twitchin, or with phosphorylated twitchin; with or without phalloidin-stabilized F-actin; and at various Ca(2+) concentrations. At low Ca(2+) concentration, Mg-ATPase was activated by F-actin only in the presence of dephosphorylated twitchin (catch state). The activation was about two orders lower than that fully activated by Ca(2+) and F-actin. In the absence of F-actin, twitchin and its phosphorylation state did not affect Mg-ATPase activities in any of the conditions we tested. Based on these results, we propose a molecular mechanism for the catch, where twitchin alone does not interact with the myosin catalytic motor domain but its complex with F-actin does, forming the bridge between actin and myosin filaments and the myosin slowly hydrolyzes Mg-ATP in the catch state.
软体动物肌抽搐,一种与肌联蛋白/伴肌球蛋白相关的巨大蛋白,在低 Ca(2+)浓度下调节肌动蛋白丝和肌球蛋白丝之间的相互作用。当它去磷酸化时,肌动蛋白丝紧密结合到肌球蛋白丝上,导致高被动张力状态,即能量消耗非常低的状态。然而,当肌抽搐被磷酸化时,肌动蛋白丝从肌球蛋白丝上脱离,导致肌肉松弛。在这里,在各种条件下测量了纯化肌球蛋白的稳态 Mg-ATP 酶活性:没有肌抽搐、去磷酸化肌抽搐或磷酸化肌抽搐;有或没有鬼笔环肽稳定的 F-肌动蛋白;以及不同的 Ca(2+)浓度。在低 Ca(2+)浓度下,只有在去磷酸化肌抽搐(捕捉状态)存在的情况下,F-肌动蛋白才能激活 Mg-ATP 酶。这种激活比 Ca(2+)和 F-肌动蛋白完全激活的活性低两个数量级左右。在没有 F-肌动蛋白的情况下,在我们测试的所有条件下,肌抽搐及其磷酸化状态都不会影响 Mg-ATP 酶活性。基于这些结果,我们提出了一种捕捉的分子机制,其中肌抽搐本身不与肌球蛋白催化马达结构域相互作用,但它与 F-肌动蛋白的复合物与之相互作用,在肌动蛋白丝和肌球蛋白丝之间形成桥,并使肌球蛋白在捕捉状态下缓慢水解 Mg-ATP。