Membrane transport mechanisms

The function of cells and organelle depend on the transport of diverse molecules across the biological membrane. When the molecules move along a concentration gradient, the chemical potential energy itself could drive the transport. However, membrane transporters often carry substrates against a concentration gradient. In order to overcome such an energy barrier, they couple an external energy source with substrate translocation. Depending on the transporter, the energy may be provided by ATP, electrochemical gradient, or light. In our group, we study ATP Binding Cassette (ABC) transporters  (collaboration with Tampé Group) and another proton-coupled secondary transporter (SLC26Dg, in collaboration with Geertsma Group). Specifically, we address how the energy from ATP hydrolysis or proton gradient is coupled to conformational changes and substrate translocation. 

Related Publications:

  1. Chang YN, Jaumann EA, Reichel K, Hartmann J, Oliver D, Hummer G*, Joseph B*, Geertsma ER* (2019) Structural basis for functional interaction in dimers of SLC26 transporters. Nat. Commun., in press (*corresponding authors)

  2. Barth K, Hank S, Spindler PE, Prisner TF, Tampé R, Joseph B* (2018) Conformational Coupling and trans-Inhibition in the Human Antigen Transporter Ortholog TmrAB Resolved with Dipolar EPR Spectroscopy. J. Am. Chem. Soc., 140, 4527–4533. (*corresponding author)

  3. Bock C, Löhr F, Tumulka F, Reichel K, Würz J, Hummer G, Schäfer L, Tampé R, Joseph B, Bernhard F, Dötsch V, Abele R. Structural and functional insights into the interaction and targeting hub TMD0 of the polypeptide transporter TAPL (2018). Sci. Rep., 8(1):15662.

  4. Nöll A, Thomas C, Herbring V, Zollmann T, Barth K, Mehdipour AR, Tomasiak TM, Brüchert S, Joseph B, Abele R, Oliéric V, Wang M, Diederichs K, Hummer G, Stroud RM, Pos KM, and Tampé R (2017) Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP. Proc. Natl. Acad. Sci. USA., 114,
    E438-447.

  5. Joseph B, Korkhov VM, Yulikov M, Jeschke G, Bordignon E (2014) Conformational cycle of the vitamin B12 ABC importer in liposomes detected by double electron-electron resonance (DEER). J. Biol. Chem., 289, 3176-3185.

  6. Doll A, Bordignon E, Joseph B, Tschaggelar R, Jeschke G (2012) Liquid state DNP for water accessibility measurements on spin-labeled membrane proteins at physiological temperatures. J. Magn. Reson., 222, 34-43.

  7. Joseph B, Jeschke G, Goetz BA, Locher KP, Bordignon E (2011) Transmembrane gate movements in type II ATP-binding cassette (ABC) importer BtuCD-F during nucleotide cycle. J. Biol. Chem., 286, 41008-41017.