Electron-transferring flavoproteins (ETFs) from human and Paracoccus denitr
ificans have been analyzed by small angle x-ray scattering, showing that ne
ither molecule exists in a rigid conformation in solution. Both ETFs sample
a range of conformations corresponding to a large rotation of domain II wi
th respect to domains I and III. A model of the human ETF-medium chain acyl
-CoA dehydrogenase complex, consistent with x-ray scattering data, indicate
s that optimal electron transfer requires domain Il of ETF to rotate by sim
ilar to 30 to 50 degrees toward domain I relative to its position in the x-
ray structure. Domain motion establishes a new "robust engineering principl
e" for electron transfer complexes, tolerating multiple configurations of t
he complex while retaining efficient electron transfer.