Influence of Structural Symmetry on Protein Dynamics

Structural symmetry in homooligomeric proteins has intrigued many researchers over the past several decades. However, the implication of protein symmetry is still not well understood. In this study, we performed molecular dynamics (MD) simulations of two forms of trp RNA binding attenuation protein (TRAP), the wild-type 11-mer and an engineered 12-mer, having two different levels of circular symmetry. The results of the simulations showed that the inter-subunit fluctuations in the 11-mer TRAP were significantly smaller than the fluctuations in the 12-mer TRAP while the internal fluctuations were larger in the 11-mer than in the 12-mer. These differences in thermal fluctuations were interpreted by normal mode analysis and group theory. For the 12-mer TRAP, the wave nodes of the normal modes existed at the flexible interface between the subunits, while the 11-mer TRAP had its nodes within the subunits. The principal components derived from the MD simulations showed similar mode structures. These results demonstrated that the structural symmetry was an important determinant of protein dynamics in circularly symmetric homooligomeric proteins.近几十年来，同源寡聚蛋白（homooligomeric proteins）的结构对称性一直是诸多研究者关注的热点课题。然而，人们对于蛋白质对称性的生物学内涵仍未形成充分透彻的认知。本研究针对两种具有不同圆形对称性水平的色氨酸RNA结合衰减蛋白（trp RNA binding attenuation protein, TRAP）变体开展分子动力学（molecular dynamics, MD）模拟：野生型11聚体与工程化改造的12聚体。模拟结果显示，11聚体TRAP的亚基间涨落显著小于12聚体TRAP，而其亚基内部涨落则高于12聚体TRAP。研究通过简正模式分析（normal mode analysis）与群论（group theory）对上述热涨落差异进行了解释：12聚体TRAP的简正模式波节位于亚基间的柔性界面处，而11聚体TRAP的波节则位于亚基内部。由分子动力学模拟得到的主成分同样呈现出相似的模式结构。上述结果表明，结构对称性是圆形对称同源寡聚蛋白动力学特性的重要决定因素。