Wako Hiroshi, Endo Shigeru
School of Social Sciences, Waseda University, Shinjuku-ku, Tokyo 169-8050, Japan.
Department of Physics, School of Science, Kitasato University, Sagamihara, Kanagawa 252-0373, Japan.
Biophys Physicobiol. 2019 Nov 29;16:220-231. doi: 10.2142/biophysico.16.0_220. eCollection 2019.
Dynamics of oligomeric proteins (one trimer, two tetramers, and one hexamer) were studied by elastic network model-based normal mode analysis to characterize their large-scale concerted motions. First, the oligomer motions were simplified by considering rigid-body motions of individual subunits. The subunit motions were resolved into three components in a cylindrical coordinate system: radial, tangential, and axial ones. Single component is dominant in certain normal modes. However, more than one component is mixed in others. The subunits move symmetrically in certain normal modes and as a standing wave with several wave nodes in others. Secondly, special attention was paid to atoms on inter-subunit interfaces. Their displacement vectors were decomposed into intra-subunit deformative (internal) and rigid-body (external) motions in individual subunits. The fact that most of the cosines of the internal and external motion vectors were negative for the atoms on the inter-subunit interfaces, indicated their opposing movements. Finally, a structural network of residues defined for each normal mode was investigated; the network was constructed by connecting two residues in contact and moving coherently. The centrality measure "betweenness" of each residue was calculated for the networks. Several residues with significantly high betweenness were observed on the inter-subunit interfaces. The results indicate that these residues are responsible for oligomer dynamics. It was also observed that amino acid residues with significantly high betweenness were more conservative. This supports that the betweenness is an effective characteristic for identifying an important residue in protein dynamics.
通过基于弹性网络模型的正则模式分析研究了寡聚蛋白(一个三聚体、两个四聚体和一个六聚体)的动力学,以表征其大规模协同运动。首先,通过考虑单个亚基的刚体运动简化了寡聚体运动。亚基运动在柱坐标系中分解为三个分量:径向、切向和轴向分量。在某些正则模式中单个分量占主导。然而,在其他模式中不止一个分量混合在一起。亚基在某些正则模式中对称移动,而在其他模式中则以具有多个波节的驻波形式移动。其次,特别关注亚基间界面上的原子。它们的位移矢量在各个亚基中分解为亚基内变形(内部)和刚体(外部)运动。亚基间界面上的原子的内部和外部运动矢量的余弦大多为负这一事实表明它们的运动方向相反。最后,研究了为每个正则模式定义的残基结构网络;该网络通过连接相互接触并协同移动的两个残基构建而成。计算了网络中每个残基的中心性度量“介数”。在亚基间界面上观察到几个介数显著较高的残基。结果表明这些残基负责寡聚体动力学。还观察到介数显著较高的氨基酸残基更保守。这支持介数是识别蛋白质动力学中重要残基的有效特征。