Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Biophys J. 2010 Sep 8;99(5):1596-603. doi: 10.1016/j.bpj.2010.06.032.
Alpha-solenoid proteins are suggested to constitute highly flexible macromolecules, whose structural variability and large surface area is instrumental in many important protein-protein binding processes. By equilibrium and nonequilibrium molecular dynamics simulations, we show that importin-beta, an archetypical alpha-solenoid, displays unprecedentedly large and fully reversible elasticity. Our stretching molecular dynamics simulations reveal full elasticity over up to twofold end-to-end extensions compared to its bound state. Despite the absence of any long-range intramolecular contacts, the protein can return to its equilibrium structure to within 3 A backbone RMSD after the release of mechanical stress. We find that this extreme degree of flexibility is based on an unusually flexible hydrophobic core that differs substantially from that of structurally similar but more rigid globular proteins. In that respect, the core of importin-beta resembles molten globules. The elastic behavior is dominated by nonpolar interactions between HEAT repeats, combined with conformational entropic effects. Our results suggest that alpha-solenoid structures such as importin-beta may bridge the molecular gap between completely structured and intrinsically disordered proteins.
α-螺旋束蛋白被认为是构成高度灵活的大分子，其结构的可变性和较大的表面积在许多重要的蛋白质-蛋白质结合过程中起着重要作用。通过平衡和非平衡分子动力学模拟，我们表明，importin-β，一种典型的α-螺旋束蛋白，表现出前所未有的大的和完全可逆的弹性。我们的拉伸分子动力学模拟表明，与结合态相比，该蛋白在长达两倍的末端延伸时具有完全的弹性。尽管没有任何长程分子内接触，该蛋白在机械应力释放后可以在 3A 骨架 RMSD 内恢复到其平衡结构。我们发现，这种极端的柔韧性基于一个异常灵活的疏水性核心，与结构相似但更刚性的球状蛋白有很大的不同。在这方面，importin-β 的核心类似于无规卷曲。弹性行为主要由 HEAT 重复之间的非极性相互作用以及构象熵效应决定。我们的结果表明，像 importin-β 这样的α-螺旋束结构可能在完全结构和固有无序的蛋白质之间架起分子的桥梁。
