This title appears in the Scientific Report :
2021
Please use the identifier:
http://hdl.handle.net/2128/28799 in citations.
Please use the identifier: http://dx.doi.org/10.3390/ijms221910345 in citations.
Computational Analyses of the AtTPC1 (Arabidopsis Two-Pore Channel 1) Permeation Pathway
Computational Analyses of the AtTPC1 (Arabidopsis Two-Pore Channel 1) Permeation Pathway
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 repo...
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Personal Name(s): | Navarro-Retamal, Carlos (Corresponding author) |
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Schott, Stephan / Gohlke, Holger (Corresponding author) / Dreyer, Ingo (Corresponding author) | |
Contributing Institute: |
Bioinformatik; IBG-4 Strukturbiochemie; IBI-7 John von Neumann - Institut für Computing; NIC Jülich Supercomputing Center; JSC |
Published in: | International journal of molecular sciences, 22 (2021) 19, S. 10345 - |
Imprint: |
Basel
Molecular Diversity Preservation International
2021
|
DOI: |
10.3390/ijms221910345 |
Document Type: |
Journal Article |
Research Program: |
SFB 1208: Identität und Dynamik von Membransystemen - von Molekülen bis zu zellulären Funktionen Forschergruppe Gohlke Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups Utilization of renewable carbon and energy sources and engineering of ecosystem functions Biological and environmental resources for sustainable use |
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Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.3390/ijms221910345 in citations.
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. |