Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin
Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin
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DOI：
10.1073/pnas.1105734108
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发表时间：
2011-08-23
影响因子：
11.1
通讯作者：
Rief, Matthias
中科院分区：
文献类型：
--
作者：
Berkemeier, Felix;Bertz, Morten;Rief, Matthias
肌肉高度定向的丝状蛋白网络在肌肉运行过程中不断经历显著的机械负荷。二聚体肌凝蛋白已被确定为支持整个肌节机械完整性的重要m波段成分。最近的结构研究发现，在肌球蛋白的c端免疫球蛋白（Ig）结构域My12和My13之间存在一个长α -螺旋连接体。在本文中，我们使用单分子力谱结合分子动力学模拟来表征包含免疫球蛋白结构域My12-My13的肌溶酶二聚体的机制。我们发现，在大约30 pN的力下，a-螺旋连接器可逆地延长，使分子的延伸超过整个结构域的折叠延伸。高分辨率测量直接揭示了单个螺旋的平衡折叠/展开动力学。我们表明，a-螺旋展开机械保护分子同源二聚化从离解在生理相关的力量。作为快速可逆的分子弹簧，肌球蛋白α -螺旋连接体是M带结构完整性的重要组成部分。
The highly oriented filamentous protein network of muscle constantly experiences significant mechanical load during muscle operation. The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studies have revealed a long alpha-helical linker between the C-terminal immunoglobulin (Ig) domains My12 and My13 of myomesin. In this paper, we have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12-My13. We find that at forces of approximately 30 pN the a-helical linker reversibly elongates allowing the molecule to extend by more than the folded extension of a full domain. High-resolution measurements directly reveal the equilibrium folding/unfolding kinetics of the individual helix. We show that a-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. As fast and reversible molecular springs the myomesin alpha-helical linkers are an essential component for the structural integrity of the M band.