Solute carrier transporters (SLCs) limit receptor activation via uptake of extracellular ligands. Novel concepts are emerging that describe the modulation of intracellular and plasma membrane... Show moreSolute carrier transporters (SLCs) limit receptor activation via uptake of extracellular ligands. Novel concepts are emerging that describe the modulation of intracellular and plasma membrane receptors by ligand influx and efflux via SLCs, respectively. Here, we evaluate recent insights and provide an outlook for developing potential therapeutic strategies. Show less
Bacterial chemosensory arrays are protein assemblies that are the key structural and functional component for motile bacteria to sense their internal or environmental chemical signals. Cryo... Show moreBacterial chemosensory arrays are protein assemblies that are the key structural and functional component for motile bacteria to sense their internal or environmental chemical signals. Cryo electron tomography is a technique of transmission electron microscopy that allows the visualization of protein complexes in their near-native cellular context. This thesis includes a general introduction of the basics of bacterial chemosensory and the structural diversity of chemosensory arrays, as well as a description of the workflow of using cryo electron tomography to image bacterial chemosensory arrays in situ. This thesis presents the discovery of a different stoichiometry of chemotaxis proteins and a direct visualization of the kinase distribution within the chemosensory arrays in Vibrio cholerae. This highlight that a structural diversity of chemoreceptor arrays does exist, and that is the norm and not an exception. This thesis also includes studies illustrating the conformational dynamics of the Escherichia coli chemoreceptors correlated to its signaling states, which gives crucial insights on how the receptors function in a trimers-of-dimers packing arrangement. In short, studies present here broaden the appreciation of the structural diversity of chemosensory arrays and deepen our understanding of how arrays dynamically functions during chemosensory signal transduction. Show less
Klop, B.; Pol, P. van der; Bruggen, R. van; Wang, Y.A.; Vries, M.A. de; Santen, S. van; ... ; Cabezas, M.C. 2014