ETF-QO consists of one structural domain with three functional domains packed in close proximity: a FAD domain, a 4Fe4S cluster domain, and a UQ-binding domain. FAD is in an extended conformation and is buried deeply within its functional domain. Multiple hydrogen bonds and a positive helix dipole modulate the redox potential of FAD and can possibly stabilize the anionic semiquinone intermediate. The 4Fe4S cluster is also stabilized by extensive hydrogen bonding around the cluster and its cysteine components. Ubiquinone binding is achieved through a deep hydrophobic binding pocket which is a different mode than other UQ-binding proteins such as succinate-Q oxidoreductase. Although ETF-QO is an integral membrane protein, it does not traverse the entire membrane unlike other UQ-binding proteins.