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

摘要

Cellular energy production depends on electron transfer (ET) betweenproteins. In this theoretical study, we investigate the impact of structuraland conformational variations on the electronic coupling between the redoxproteins methylamine dehydrogenase and amicyanin from Paracoccus denitrificans.We used molecular dynamics simulations to generate configurations over aduration of 40ns (sampled at 100fs intervals) in conjunction with an ET pathwayanalysis to estimate the ET coupling strength of each configuration. In thewild type complex, we find that the most frequently occurring molecularconfigurations afford superior electronic coupling due to the consistentpresence of a water molecule hydrogen-bonded between the donor and acceptorsites. We attribute the persistence of this water bridge to a "molecularbreakwater" composed of several hydrophobic residues surrounding the acceptorsite. The breakwater supports the function of nearby solvent-organizingresidues by limiting the exchange of water molecules between the stericallyconstrained ET region and the more turbulent surrounding bulk. When thebreakwater is affected by a mutation, bulk solvent molecules disrupt the waterbridge, resulting in reduced electronic coupling that is consistent with recentexperimental findings. Our analysis suggests that, in addition to enabling theassociation and docking of the proteins, surface residues stabilize and controlinterprotein solvent dynamics in a concerted way.