EMBO long-term fellowship for the study on the Energy-cpupling factor ECF in the GBB research group Membrane Enzymology under supervision of Prof.dr. D.J. Slotboom.
The current proposal aims at the study of energy-coupling factor (ECF) transporters responsible for the uptake of vitamins in Gram-positive (pathogenic) bacteria. These transporters have two unique features which make them ideal to address basic questions about membrane protein function: First, ECF transporters use an integral membrane complex (the energizing module) that is shared in a competitive manner by many small integral membrane proteins (S-components), which bind different vitamin substrates. Thus the proteins can be used to study protein-protein interactions in lipid bilayers, a poorly understood process. Second, the S-components are hypothesized to topple over in the membrane during transport to bring the substrate from one side to the other. Toppling is unprecedented among known membrane proteins and -if confirmed- extends the dynamic and functional capacities of membrane proteins dramatically. In addition, because vitamin uptake is essential in many pathogenic bacteria the proteins might be suitable targets for novel antimicrobial agents.
The goal of this proposal is to elucidate the dynamics of substrate transport across the membrane, as well as the arrangement and interactions within different ECF complexes. Such an approach will ultimately help to build a detailed picture of this unique class of membrane proteins and help create new therapeutic avenues that target specifically ECF transporters.