Residue interaction chains facilitating the structural change of ND6 subunit in respiratory complex I

Respiratory complex I generates proton gradient through coupled NADH: ubiquinone oxidoreduction and proton pumping for ATP synthesis in aerobic respiration. Structural studies showed the involvement of the third transmembrane helix in ND6 subunit (TMH3_ND6) in the global open-closed conformational change of RCI was important for the functional coupling. However, the atomistic mechanism for the conformational change of TMH3_ND6 remains unclear. Here, we computationally analyzed the network graphs of coevolving residue contacts of the core functional subunits derived from Escherichia coli and Ovis aries. We identified four conserved paths connecting the quinone-binding site and TMH3_ND6. Together with structural frustration and genomic variant analyses, we suggest that these paths can transmit structural disturbance upon quinone binding, facilitating the conformational change of TMH3_ND6.