Phosphorylated Smooth Muscle Heavy Meromyosin Shows an Open Conformation Linked to Activation
Phosphorylated Smooth Muscle Heavy Meromyosin Shows an Open Conformation Linked to Activation
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DOI：
10.1016/j.jmb.2011.10.047
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发表时间：
2012-01-13
影响因子：
5.6
通讯作者：
Taylor, Kenneth A.
中科院分区：
文献类型：
--
作者：
Baumann, Bruce A. J.;Taylor, Dianne W.;Taylor, Kenneth A.
平滑肌肌球蛋白和平滑肌重酶解肌球蛋白（smHMM）通过调节性轻链磷酸化激活，但其机制尚不清楚。去磷酸化的，无活性的smHMM呈现封闭构象，马达结构域之间具有不对称的分子内头-头相互作用。“自由头”可以结合肌动蛋白，但“封闭头”的肌动蛋白结合界面参与与自由头的相互作用。在这里，我们报告了一个三维结构的磷酸化，活性smHMM获得使用电子晶体学的二维阵列。磷酸化的smHMM的头-头相互作用类似于在去磷酸化状态下发现的那些，但发生在不同的分子之间，而不是在同一个分子内。磷酸化smHMM的轻链结合结构域结构与去磷酸化smHMM的“封闭”头部结构明显不同。我们推测，调节轻链磷酸化打开抑制的构象主要是通过其对受阻的头部的影响。如果封闭的头部被磷酸化，则单独磷酸化的smHMM与闭合构象不相容。这一概念对平滑肌中低水平磷酸化时肌球蛋白激活的程度有影响。(C)2011爱思唯尔有限公司保留所有权利。
Smooth muscle myosin and smooth muscle heavy meromyosin (smHMM) are activated by regulatory light chain phosphorylation, but the mechanism remains unclear. Dephosphorylated, inactive smHMM assumes a closed conformation with asymmetric intramolecular head head interactions between motor domains. The "free head" can bind to actin, but the actin binding interface of the "blocked head" is involved in interactions with the free head. We report here a three-dimensional structure for phosphorylated, active smHMM obtained using electron crystallography of two-dimensional arrays. Head head interactions of phosphorylated smHMM resemble those found in the dephosphorylated state but occur between different molecules, not within the same molecule. The light chain binding domain structure of phosphorylated smHMM differs markedly from that of the "blocked" head of dephosphorylated smHMM. We hypothesize that regulatory light chain phosphorylation opens the inhibited conformation primarily by its effect on the blocked head. Singly phosphorylated smHMM is not compatible with the closed conformation if the blocked head is phosphorylated. This concept has implications for the extent of myosin activation at low levels of phosphorylation in smooth muscle. (C) 2011 Elsevier Ltd. All rights reserved.