Graph-Theoretical Prediction and Analysis of Biologically Relevant Substructures in an Open and Closed Conformation...

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.