Golji Javad, Collins Robert, Mofrad Mohammad R K
Molecular Cell Biomechanics Laboratory, University of California Berkeley, Berkeley, California, USA.
PLoS Comput Biol. 2009 May;5(5):e1000389. doi: 10.1371/journal.pcbi.1000389. Epub 2009 May 15.
alpha-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks. As a crosslinker in the stressed cytoskeleton, alpha-actinin can retain conformation, function, and strength. alpha-Actinin has an actin binding domain and a calmodulin homology domain separated by a long rod domain. Using molecular dynamics and normal mode analysis, we suggest that the alpha-actinin rod domain has flexible terminal regions which can twist and extend under mechanical stress, yet has a highly rigid interior region stabilized by aromatic packing within each spectrin repeat, by electrostatic interactions between the spectrin repeats, and by strong salt bridges between its two anti-parallel monomers. By exploring the natural vibrations of the alpha-actinin rod domain and by conducting bending molecular dynamics simulations we also predict that bending of the rod domain is possible with minimal force. We introduce computational methods for analyzing the torsional strain of molecules using rotating constraints. Molecular dynamics extension of the alpha-actinin rod is also performed, demonstrating transduction of the unfolding forces across salt bridges to the associated monomer of the alpha-actinin rod domain.
α-辅肌动蛋白是一种肌动蛋白交联分子,可作为支架并维持动态肌动蛋白丝网络。作为应激细胞骨架中的交联剂,α-辅肌动蛋白可保持构象、功能和强度。α-辅肌动蛋白具有一个肌动蛋白结合结构域和一个钙调蛋白同源结构域,由一个长杆状结构域隔开。通过分子动力学和正常模式分析,我们认为α-辅肌动蛋白杆状结构域具有灵活的末端区域,在机械应力下可扭曲和伸展,但其内部区域高度刚性,通过每个血影蛋白重复序列内的芳香堆积、血影蛋白重复序列之间的静电相互作用以及其两个反平行单体之间的强盐桥得以稳定。通过探索α-辅肌动蛋白杆状结构域的自然振动并进行弯曲分子动力学模拟,我们还预测杆状结构域只需最小的力就可能发生弯曲。我们介绍了使用旋转约束分析分子扭转应变的计算方法。还进行了α-辅肌动蛋白杆的分子动力学扩展,证明了展开力通过盐桥传递到α-辅肌动蛋白杆状结构域的相关单体。