Surface residues dynamically organize water bridges to enhance electron transfer between proteins

Efficient, directed electron transfer between proteins is an important part of metabolic processes, but how does the electron cross the inter-protein abyss? To answer this question, we study electronic coupling between the reduction-oxidation proteins methylamine dehydrogenase and amicyanin from Paracoccus denitrificans. This protein complex has been studied crystallographically thereby providing an initial condition for molecular dynamics simulations. Furthermore electron coupling is known for the wild type and for some mutants thereby enabling empirical quantitative studies of the electron transfer rate subject to protein-surface modifications. We discover that, in the wild type, the most frequently occurring molecular configurations afford superior electronic coupling due to the presence of a water molecule hydrogen-bonded between the donor and acceptor sites of the two proteins, and we attribute the persistence of this water bridge to a protective molecular breakwater comprising hydrophobic residues surrounding the acceptor site. In mutants bulk solvent molecules disrupt the water bridge thereby resulting in reduced electronic coupling consistent with experimental findings. We conclude that the protein's surface residues enable association and docking of proteins for electron transfer, and the residues also stabilize and control inter-protein solvent dynamics to build a water bridge for efficient electron transport.