Goethe University Frankfurt, Molecular Bioinformatics, Institute of Computer Science, Faculty of Computer Science and Mathematics, Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
Methods Mol Biol. 2025;2870:289-314. doi: 10.1007/978-1-0716-4213-9_15.
Protein complexes are functional modules within the hierarchy of the cellular organization. Large protein complexes often consist of smaller functional modules, which are biologically relevant substructures with specific functions. The first protein complex of the respiratory chain, complex I, consists of functional modules for the electron transfer from NADH to quinone and the translocation of protons across the inner mitochondrial membrane. Complex I is well-characterized and biological modules have been experimentally assigned. Nevertheless, there is an ongoing discussion about the coupling of the electron transfer and the proton translocation, and about the proton translocation pathways.We modelled a mammalian complex I in open and closed conformations as complex graphs, with vertices representing protein chains and edges representing chain-chain contacts. Using a graph-theoretical method, we computed the structural modules of complex I, which indicated functional, biological substructures. We described characteristic structural features of complex I and observed a rearrangement of the structural modules. The changes in the structural modules indicated the formation of a functional module in the membrane arm of complex I during the conformational change.
蛋白质复合物是细胞组织层次结构中的功能模块。大型蛋白质复合物通常由较小的功能模块组成，这些模块是具有特定功能的生物学相关亚结构。呼吸链的第一个蛋白质复合物 I，由从 NADH 到醌的电子转移和质子穿过线粒体内膜的跨膜转运的功能模块组成。复合物 I 具有很好的特征，并且已经实验性地分配了生物模块。然而，关于电子转移和质子转运的偶联，以及质子转运途径，仍存在持续的讨论。我们将哺乳动物的复合物 I 以开放和闭合构象建模为复杂图，其中顶点代表蛋白质链，边代表链链接触。使用图论方法，我们计算了复合物 I 的结构模块，这表明了功能和生物学的亚结构。我们描述了复合物 I 的特征结构特征，并观察到结构模块的重排。结构模块的变化表明在构象变化过程中复合物 I 的膜臂中形成了一个功能模块。
