Transporters

Membrane transporters mediate the translocation of a plethora of substrates with different chemical and physical properties ranging from a single metal ion to large biological complexes. The fundamental role in regulating cellular homeostasis has made them an interesting target for therapies against several and severe diseases. In the MeilerLab we tackle the investigation of transporters by exploiting in-house technologies and our researchers’ expertise. Here, three transporters are listed we have studied in the past: type III secreted phospholipase effector [1] (ExoU), translocator protein [2] (TSPO) and the small multidrug transporter [3] (EmrE).

Figure 1: Transport across the membrane shown for influx and efflux.

References:
[1] Tessmer, M. H.; DeCero, S. A.; del Alamo, D.; Riegert, M. O.; Meiler, J.; Frank, D. W.; Feix, J. B. Characterization of the ExoU Activation Mechanism Using EPR and Integrative Modeling. Sci. Rep. 2020, 10. https://doi.org/10.1038/s41598-020-76023-3.
[2] Xia, Y.; Ledwitch, K.; Kuenze, G.; Duran, A.; Li, J.; Sanders, C. R.; Manning, C.; Meiler, J. A Unified Structural Model of the Mammalian Translocator Protein (TSPO). J. Biomol. NMR 2019, 73, 347–364. https://doi.org/10.1007/s10858-019-00257-1.
[3] Dastvan, R.; Fischer, A. W.; Mishra, S.; Meiler, J.; McHaourab, H. S. Protonation-Dependent Conformational Dynamics of the Multidrug Transporter EmrE. Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 1220–1225. https://doi.org/10.1073/pnas.1520431113.