Functional impact of transmembrane domain and turret on potassium channel gating

Final Report Abstract

The project has produced interesting results regarding: a) A so far unknown mechanism for a cytosolic gate in K+ channels that particularly stands out because of its unusual simplicity. b) A novel concept of regulation of gating by voltage. In the absence of a dedicated voltage-sensor domain, the extracellular turret is apparently able to confer voltagesensitivity. c) The possibility to determined site-specific ion occupation in the pore from electrophysiological data, which enabled the distinction of several candidate permeation models from MD simulations and the identification of a distinct sensor binding site in the selectivity filter. Additionally, the project generated incentive for new projects regarding the role of inner-helical hydrogen bonds for channel gating and the mechanisms of selectivity filter gating.

Publications

• 2015. How to resolve microsecond current fluctuations in single ion channels: The power of beta distributions. Channels. 9: 262–280
  Schroeder, I.
  
• 2016. A simple recipe for setting up the flux equations of cyclic and linear reaction schemes of ion transport with a high number of states: the arrow scheme. Channels. 10: 1–20
  Hansen, U.-P., O. Rauh, and I. Schroeder
  
• 2017. Extended beta distributions open the access to fast gating in bilayer experiments-assigning the voltage-dependent gating to the selectivity filter. FEBS Lett. 591: 3850–3860
  Rauh, O., U.-P. Hansen, S. Mach, A.J.W. Hartel, K.L. Shepard, G. Thiel, and I. Schroeder
  
• 2017. Identification of intra-helical bifurcated H-bonds as a new type of gate in K+ channels. J. Am. Chem. Soc. 139: 7494–7503
  Rauh, O., M. Urban, L.M. Henkes, T. Winterstein, T. Greiner, J.L. Van Etten, A. Moroni, S.M. Kast, G. Thiel, and I. Schroeder
  
• 2018. Molecular explanations for gating in simple model K+ channels. PhD thesis, Tech. Univ. Darmstadt
  Rauh, O.
  
• 2018. Reconstitution and functional characterization of ion channels from nanodiscs in lipid bilayers. J. Gen. Physiol. 150: 637–646
  Winterstein, L.-M., K. Kukovetz, O. Rauh, D.L. Turman, C.J. Braun, A. Moroni, I. Schroeder, and G. Thiel
  
• 2018. Single-channel recordings of RyR1 at microsecond resolution in CMOS-suspended membranes. Proc. Natl. Acad. Sci. 115: E1789–E1798
  Hartel, A.J.W., P. Ong, I. Schroeder, M.H. Giese, S. Shekar, O.B. Clarke, R. Zalk, A.R. Marks, W.A. Hendrickson, and K.L. Shepard
  
• 2018. Site-specific ion occupation in the selectivity filter causes voltage-dependent gating in a viral K+ channel. Sci. Rep. 8: 10406
  Rauh, O., U.P. Hansen, D.D. Scheub, G. Thiel, and I. Schroeder
  
• 2019. High bandwidth approaches in nanopore and ion channel recordings - A tutorial review. Anal. Chim. Acta. 1061: 13–27
  Andreas Hartel, S. Shekar, P. Ong, I. Schroeder, G. Thiel, and K.L. Shepard