Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil.
Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil.
复制标题
原肌球蛋白卷曲螺旋功能不同区域的弹性调节。
DOI：
10.1007/s12195-009-0050-1
复制
发表时间：
2009
影响因子：
2.8
通讯作者：
Hwang,Wonmuk
中科院分区：
文献类型：
--
作者：
Lakkaraju,SirishKaushik;Hwang,Wonmuk
α-螺旋卷曲螺旋是常见的蛋白质结构基序。尽管关于它们的结构、折叠和稳定性有大量的信息，但关于它们的弹性性质知之甚少，尽管它们在许多情况下起着机械作用，如原肌球蛋白在肌肉收缩中或驱动蛋白或肌球蛋白马达蛋白的颈柄中。使用计算机模拟，我们的特点是弹性性能的线圈线圈，无论是全球或局部。使用简正模态分析计算标准亮氨酸拉链线圈的整体弯曲刚度。两个α-螺旋之间的节-孔界面中涉及的疏水残基的突变显著影响弹性，而形成螺旋间盐桥的带电侧链则不会。这表明具有不太规则的七肽周期性的卷曲螺旋可能具有灵活性的区域变化。我们表明这一点的灵活性地图的原肌球蛋白，这是由当地的波动分析。总的来说，柔性变化超过两倍，并且朝向分子的C-末端区域增加。将盘绕线圈描述为扭曲带，其通常在展开弯曲中比在宽面弯曲中更柔韧。α区的肌动蛋白结合位点表现出局部刚性极小值。断裂的核心区域，由于酸性残基在疏水面，如Asp 137和Glu 218被认为是最不稳定的，与模量为116和68 nm，分别为展曲和宽面弯曲。这种灵活性的变化可能与原肌球蛋白的功能有关，特别是在F-肌动蛋白的非均匀表面上移动以调节肌球蛋白结合。
Alpha-helical coiled-coils are common protein structural motifs. Whereas vast information is available regarding their structure, folding, and stability, far less is known about their elastic properties, even though they play mechanical roles in many cases such as tropomyosin in muscle contraction or neck stalks of kinesin or myosin motor proteins. Using computer simulations, we characterized elastic properties of coiled-coils, either globally or locally. Global bending stiffness of standard leucine zipper coiled-coils was calculated using normal mode analysis. Mutations in hydrophobic residues involved in the knob-into-hole interface between the two α-helices affect elasticity significantly, whereas charged side chains forming inter-helical salt bridges do not. This suggests that coiled-coils with less regular heptad periodicity may have regional variations in flexibility. We show this by the flexibility map of tropomyosin, which was constructed by a local fluctuation analysis. Overall, flexibility varies by more than twofold and increases toward the C-terminal region of the molecule. Describing the coiled-coil as a twisted tape, it is generally more flexible in the splay bending than in the bending of the broad face. Actin binding sites in α zones show local rigidity minima. Broken core regions due to acidic residues at the hydrophobic face such as the Asp137 and the Glu218 are found to be the most labile with moduli for splay and broad face bending as 116 and 68 nm, respectively. Such variation in flexibility could be relevant to the tropomyosin function, especially for moving across the non-uniform surface of F-actin to regulate myosin binding.