Conserved Intramolecular Interactions Maintain Myosin Interacting-Heads Motifs Explaining Tarantula Muscle Super-Relaxed State Structural Basis
Conserved Intramolecular Interactions Maintain Myosin Interacting-Heads Motifs Explaining Tarantula Muscle Super-Relaxed State Structural Basis
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DOI：
10.1016/j.jmb.2016.01.027
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发表时间：
2016-03-27
影响因子：
5.6
通讯作者：
Padron, Raul
中科院分区：
文献类型：
--
作者：
Alamo, Lorenzo;Qi, Dan;Padron, Raul
狼蛛横纹肌是一个杰出的系统，了解肌球蛋白丝的分子组织。基于冷冻电子显微镜图像和单粒子图像处理的三维重建表明，在放松状态下，肌球蛋白分子发生分子内头部相互作用，这解释了头部活动关闭的原因。通过将鸡平滑肌肌球蛋白结构刚性对接到重建获得的细丝模型通过灵活地拟合通过混合来自不同物种的结构而建立的原子模型来改进冷冻水合狼蛛粗细丝的倾斜校正的2 nm三维地图。我们使用狼蛛肌球蛋白的重链和轻链序列建立了两个重肌球蛋白相互作用头基序（IHM）的单物种同源性模型。灵活的拟合模型包括以前丢失的环，并显示五个分子内和五个分子间的相互作用，保持IHM在一个紧凑的关闭结构，形成四个螺旋轨道IHM周围的骨干。参与这些相互作用的残基是带相反电荷的，它们的序列保守性表明IHM存在于所有动物物种中。新模型PDB 3 JBH通过将非常慢的速率归因于对接的未磷酸化头部、缓慢的速率归因于磷酸化对接的头部以及快速的速率归因于磷酸化未对接的头部，解释了在放松的狼蛛肌肉中检测到的ATP周转率的结构起源。跨动物物种的分子内相互作用的保守性和双侧肌中IHM的存在表明，应该保持超松弛状态，因为它在骨骼肌、心脏肌和平滑肌中起到节省ATP的作用。(C)2016爱思唯尔有限公司版权所有
Tarantula striated muscle is an outstanding system for understanding the molecular organization of myosin filaments. Three-dimensional reconstruction based on cryo-electron microscopy images and single-particle image processing revealed that, in a relaxed state, myosin molecules undergo intramolecular head head interactions, explaining why head activity switches off. The filament model obtained by rigidly docking a chicken smooth muscle myosin structure to the reconstruction was improved by flexibly fitting an atomic model built by mixing structures from different species to a tilt-corrected 2-nm three-dimensional map of frozen-hydrated tarantula thick filament. We used heavy and light chain sequences from tarantula myosin to build a single-species homology model of two heavy meromyosin interacting-heads motifs (IHMs). The flexibly fitted model includes previously missing loops and shows five intramolecular and five intermolecular interactions that keep the IHM in a compact off structure, forming four helical tracks of IHMs around the backbone. The residues involved in these interactions are oppositely charged, and their sequence conservation suggests that IHM is present across animal species. The new model, PDB 3JBH, explains the structural origin of the ATP turnover rates detected in relaxed tarantula muscle by ascribing the very slow rate to docked unphosphorylated heads, the slow rate to phosphorylated docked heads, and the fast rate to phosphorylated undocked heads. The conservation of intramolecular interactions across animal species and the presence of IHM in bilaterians suggest that a super-relaxed state should be maintained, as it plays a role in saving ATP in skeletal, cardiac, and smooth muscles. (C) 2016 Elsevier Ltd. All rights reserved.