Struktur-Funktions-Beziehung von dreiteiligen Arzneimittel-auswärtspumpenden RND-Komplexen s (P18)

• Subject Area: Biochemistry
• Term: from 2010 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 57566863

We will investigate the structural determinants for the promiscuous substrate binding, molecular setup, and transport activity of tripartite Resistance Nodulation cell Division (RND)-type drug efflux complexes from selected Gram-negative bacteria. In the framework of the CRC 807, we aim to examine the molecular basis of multiple drug-binding phenotypes of homologue RND components and the molecular setup of tripartite assemblies from other Gram-negative bacteria by using (high-resolution) single-particle cryo-EM, solid-state NMR, EPR, and X-ray crystallography. The in vitro formation of tripartite assemblies will allow us to characterize drug transport in a reconstituted system and the use of RND efflux pump variants with altered drug binding specificity will enable the detailed analysis on the molecular basis of promiscuous drug binding. The combined results from the proposed research will provide detailed insight into the structure-function relationship of RND-type tripartite multidrug efflux complexes.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 807: Transport and Communication across Biological Membrans
• Applicant Institution: Goethe-Universität Frankfurt am Main
• Project Head: Professor Dr. Klaas Martinus Pos