Respiratory Complex 1, ND1 component

Structural evolutionary module detected by analysis of evolutionary couplings

A 3D structure of a full respiratory complex 1 from bacteria is now solved by X-ray crystallography (Nature 494; 443, 2013) and includes the structure of the previously enigmatic membrane protein component (NQO8). Based on this tour-de-force of structural biology, the authors can now propose a plausible model for how the long range conformational changes in the membrane components are coupled to the redox reactions in the non-membrane portion of the complex. Despite the lack of significant sequence similarity, the newly solved subunit NQO8 contains a half-anti-porter like fold, with similarity in 3D to a repeated module in three of the other membrane proteins in the complex. Interestingly, this 3D similarity was suggested by Hopf et al, (Cell, 149; 1607,  2012), who predicted that the ND1 subunit of human component, which is orthologous to NQO8, has a fold highly similar to that of the other complex 1 membrane components, by using a novel statistical analysis of evolutionary co-variation of sequences. 

The confirmation of this prediction by crystallographic experiment indicates that analysis of evolutionary relationships in terms of conservation of residue-residue interactions is potentially much more powerful than that the canonical analysis in terms of conservation of just single residue properties.