School of Bio Sciences and Technology, VIT University, Vellore-632014, Tamil Nadu, India.
J Theor Biol. 2012 Sep 21;309:78-87. doi: 10.1016/j.jtbi.2012.06.002. Epub 2012 Jun 18.
Transmembrane proteins serve as receptors, transporters or as enzymes. They mediate a broad range of fundamental cellular activities including signal transduction, cell trafficking and photosynthesis. In this study, we analyzed the significance of central residues in the polytopic transmembrane proteins. Each protein is represented as an undirected graph, where residues represent nodes and inter-residue interactions as the edges. Residue centrality was calculated by removing the nodes and its corresponding edges from the protein contact network. Results revealed that 80% of the predicted central residues had normalized conservation values below the mean since they were slowly evolving conserved sites. We also found that 56% of amino acids were interacting with the ligand molecules and metal ions. Predicted central residues in the polytopic transmembrane proteins were found to account for 84% of binding and active site amino acids. From mutation sensitivity analysis, it was observed that 89% of central residues had deleterious mutations whose probabilities were greater than their mean value. Interestingly, we find that z-score values of each amino acid positively correlate with the conservation scores and also with the degrees of each node. Results show that 87% of central residues are hub residues.
跨膜蛋白可作为受体、转运体或酶。它们介导广泛的基本细胞活动，包括信号转导、细胞运输和光合作用。在这项研究中，我们分析了多跨膜蛋白中中心残基的意义。每个蛋白质都表示为无向图，其中残基表示节点，残基之间的相互作用表示为边。通过从蛋白质接触网络中删除节点及其相应的边来计算残基的中心度。结果表明，由于是缓慢进化的保守位点，80%的预测中心残基的归一化保守值低于平均值。我们还发现，56%的氨基酸与配体分子和金属离子相互作用。在多跨膜蛋白中预测的中心残基占结合和活性位点氨基酸的 84%。通过突变敏感性分析，观察到 89%的中心残基发生有害突变，其概率大于平均值。有趣的是，我们发现每个氨基酸的 z 分数值与保守分数以及每个节点的度数呈正相关。结果表明，87%的中心残基是枢纽残基。
