Journal Article

FZJ-2021-03874

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Computational Analyses of the AtTPC1 (Arabidopsis Two-Pore Channel 1) Permeation Pathway

Navarro-Retamal, C. (Corresponding author) ; Schott, S.FZJ* ; Gohlke, H. (Corresponding author)FZJ* ; Dreyer, I. (Corresponding author)

2021
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/28799  doi:10.3390/ijms221910345

Abstract: Two Pore Channels (TPCs) are cation-selective voltage- and ligand-gated ion channels in membranes of intracellular organelles of eukaryotic cells. In plants, the TPC1 subtype forms the slowly activating vacuolar (SV) channel, the most dominant ion channel in the vacuolar membrane. Controversial reports about the permeability properties of plant SV channels fueled speculations about the physiological roles of this channel type. TPC1 is thought to have high Ca2+ permeability, a conclusion derived from relative permeability analyses using the Goldman–Hodgkin–Katz (GHK) equation. Here, we investigated in computational analyses the properties of the permeation pathway of TPC1 from Arabidopsis thaliana. Using the crystal structure of AtTPC1, protein modeling, molecular dynamics (MD) simulations, and free energy calculations, we identified a free energy minimum for Ca2+, but not for K+, at the luminal side next to the selectivity filter. Residues D269 and E637 coordinate in particular Ca2+ as demonstrated in in silico mutagenesis experiments. Such a Ca2+-specific coordination site in the pore explains contradicting data for the relative Ca2+/K+ permeability and strongly suggests that the Ca2+ permeability of SV channels is largely overestimated from relative permeability analyses. This conclusion was further supported by in silico electrophysiological studies showing a remarkable permeation of K+ but not Ca2+ through the open channel.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. John von Neumann - Institut für Computing (NIC)
3. Strukturbiochemie (IBI-7)
4. Bioinformatik (IBG-4)

Research Program(s):

1. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
2. 2172 - Utilization of renewable carbon and energy sources and engineering of ecosystem functions (POF4-217) (POF4-217)
3. 5111 - Domain-Specific Simulation Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
4. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)
5. DFG project 267205415 - SFB 1208: Identität und Dynamik von Membransystemen - von Molekülen bis zu zellulären Funktionen (267205415)

Appears in the scientific report 2021

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