Reversible movement of switch 1 loop of myosin determines actin interaction
Reversible movement of switch 1 loop of myosin determines actin interaction
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DOI：
10.1038/sj.emboj.7601482
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发表时间：
2007-01-10
期刊：
影响因子：
11.4
通讯作者：
Malnasi-Csizmadia, Andras
中科院分区：
文献类型：
--
作者：
Kintses, Balint;Gyimesi, Mates;Malnasi-Csizmadia, Andras
p环NTPases的保守开关1环被认为是在核苷酸结合袋和伴侣蛋白结合位点之间传递信息的中心元件。最近的结构研究已经确定了g蛋白和肌球蛋白中开关1的两种状态，但它们在转导机制中的作用尚未明确。将单个色氨酸残基引入肌球蛋白II运动结构域的开关1区，并用快速反应方法对其进行了研究。我们发现在MgADP存在的情况下，开关1存在两种动态平衡状态。肌动蛋白结合使平衡向MgADP的一种状态转移，而ATP则强烈倾向于另一种状态。根据电子冷冻显微镜和x射线晶体学结果，这些发现导致了一个特定的结构模型，其中开关1的两个状态之间的平衡常数与肌动蛋白-肌球蛋白相互作用的强度耦合。这对g蛋白和可能的p环NTPases的酶促机制具有启示意义。
The conserved switch 1 loop of P-loop NTPases is implicated as a central element that transmits information between the nucleotide-binding pocket and the binding site of the partner proteins. Recent structural studies have identified two states of switch 1 in G-proteins and myosin, but their role in the transduction mechanism has yet to be clarified. Single tryptophan residues were introduced into the switch 1 region of myosin II motor domain and studied by rapid reaction methods. We found that in the presence of MgADP, two states of switch 1 exist in dynamic equilibrium. Actin binding shifts the equilibrium towards one of the MgADP states, whereas ATP strongly favors the other. In the light of electron cryo-microscopic and X-ray crystallographic results, these findings lead to a specific structural model in which the equilibrium constant between the two states of switch 1 is coupled to the strength of the actin-myosin interaction. This has implications for the enzymatic mechanism of G-proteins and possibly P-loop NTPases in general.