We focus on the structural elucidation of membrane proteins of the Resistance Nodulation and cell Division (RND) Superfamily, to obtain molecular information on their transport mechanisms The RND protein AcrB plays a central role within the AcrA/AcrB/TolC antibiotic efflux pump from Escherichia coli. Dysfunction of this tripartite system leads to a drastic reduction of the natural resistance of the bacterium towards antibiotics, bile salts, detergents and dyes. Other RND members include the human Niemann-Pick C1 (NPC1) and Hedgehog Receptor Patched (Ptc).
A model for the transport of antibiotics mediated by AcrB over the bacterial membrane is postulated on the basis of the asymmetric structure of this protein (Seeger et al., 2006). Future research will focus on the transport mechanisms of orthologue RND transporters.
Fig. 01: Visualization of tunnels in the porter (pore) domain of the trimeric AcrB peristaltic drug efflux pump. The AcrB monomers are presented in (a) blue (loose), (b) yellow (tight) and (c) red (open). The tunnels are highlighted as green surfaces in a ribbon model of the AcrB trimer. Inset: Bound minocyclin is depicted inside a hydrophobic pocket in the tight monomer (yellow) with the observed electron density in a 2Fo-Fc electron density map contoured 1 σ The Panels on the left and right represent in each case a one third conversion of a full loose→tight→open→loose cycle.