Efficient Electron Transfer in a Protein Network Lacking Specific Interactions

In many biochemical processes, proteins need to bind partners amidst a sea of other molecules. Generally, partner selection is achieved by formation of a single-orientation complex with well-defined, short-range interactions. We describe a protein network that functions effectively in a metabolic electron transfer process but lacks such specific interactions. The soil bacterium Paracoccus denitrificans oxidizes a variety of compounds by channeling electrons into the main respiratory pathway. Upon conversion of methylamine by methylamine dehydrogenase, electrons are transported to the terminal oxidase to reduce molecular oxygen. Steady-state kinetic measurements and NMR experiments demonstrate a remarkable number of possibilities for the electron transfer, involving the cupredoxin amicyanin as well as four c-type cytochromes. The observed interactions appear to be governed exclusively by the electrostatic nature of each of the proteins. It is concluded that Paracoccus provides a pool of cytochromes for efficient electron transfer via weak, ill-defined interactions, in contrast with the view that functional biochemical interactions require well-defined molecular interactions. It is proposed that the lack of requirement for specificity in these interactions might facilitate the integration of new metabolic pathways.