2018.08.30 Membrane ion transfer underlying electric and receptor-based cell signalling

2019-07-07 00:57:18 3



    目: Membrane ion transfer underlying electric and receptor-based cell signalling

报告人:Dr. Ulrich Zachariae

Reader in Physics and Life Sciences

Deputy Head of Division, Computational Biology

Centre for Translational and Interdisciplinary Research, University of Dundee



主持人:宋晨 研究员



  Cells in higher organisms must be able to communicate both with each other and with the external world. A multitude of signalling pathways exist within eukaryotic cells, but the exchange of information across the cell membrane requires the function of specialised membrane proteins. The main routes for transmembrane signal transduction are via electric impulses, triggered by the function of ion channels, and by G-protein coupled receptor signalling.  Due to their instrumental role, these membrane proteins represent the most important and abundant drug targets in humans. In my talk, I will show how our recent molecular simulations elucidated some of the fundamental mechanisms of both, ion channel action and G-protein coupled receptor signal transmission. I will also present the molecular basis for the exquisite selectivity of ion channels, which is indispensable for the generation of sharp electric action potentials in electrically excitable cells such as neurons. Intriguingly, at the heart of both electric and receptor-based signal transduction processes, new similarities begin to emerge that entail finely controlled ion transfer processes across the cell membrane.



[1] W Kopec, DA Köpfer, ON Vickery, A Bondarenko, TLC Jansen, BL de Groot, U Zachariae: Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels. Nature Chemistry 10, 813-820 (2018)

[2] ON Vickery, CA Carvalheda, S Zaidi, AV Pisliakov, V Katritch, U Zachariae: Intracellular transfer of Na+ in an active state G-protein coupled receptor. Structure 26, 171-180 (2018).

[3] ON Vickery, JP Machtens, U Zachariae: Membrane potentials regulating GPCRs: Insights from experiments and molecular dynamics simulations. Curr. Opin. Pharmacol. 30, 44-50 (2016).

[4] DA Köpfer, C Song, T Gruene, GM Sheldrick, U Zachariae, BL de Groot: Ion permeation in K+ channels occurs by direct Coulomb knock-on. Science 346, 352-355 (2014)



  Dr. Ulrich Zachariae studied chemistry in Munich and did his Masters project in the department of Prof. Hartmut Michel at the Max Planck Institute for Biophysics in Frankfurt, where he developed a strong interest in the function of membrane proteins. He went on to do his PhD with Prof. Wolfgang Baumeister at the Max Planck Institute for Biochemistry, where he graduated in 2004. From this time onwards, Dr. Zachariae began to focus on the computational investigation of protein mechanistic questions, and he continued his research as Postdoc in the labs of Prof. Helmut Grubmüller and Prof. Bert de Groot at the Max Planck Institute in Göttingen. After conducting computational drug design on G-protein coupled receptor targets in the pharma company AstraZeneca, he became an independent PI at the University of Edinburgh in 2011, and he is currently Reader and Deputy Head of the Division of Computational Biology in the School of Life Sciences at the University of Dundee in Scotland. His research is aimed at a fundamental mechanistic understanding of the function of ion channels and G-protein coupled receptors, and the development of new antimicrobials to combat antibiotic resistance. He works closely with the Dundee Drug Discovery Unit and other experimental researchers from the fields of structural biology, physiology and microbiology.