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@ARTICLE{NavarroRetamal:901866,
author = {Navarro-Retamal, Carlos and Schott, Stephan and Gohlke,
Holger and Dreyer, Ingo},
title = {{C}omputational {A}nalyses of the {A}t{TPC}1 ({A}rabidopsis
{T}wo-{P}ore {C}hannel 1) {P}ermeation {P}athway},
journal = {International journal of molecular sciences},
volume = {22},
number = {19},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2021-03874},
pages = {10345 -},
year = {2021},
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.},
cin = {JSC / NIC / IBI-7 / IBG-4},
ddc = {540},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)IBG-4-20200403},
pnm = {2171 - Biological and environmental resources for
sustainable use (POF4-217) / 2172 - Utilization of renewable
carbon and energy sources and engineering of ecosystem
functions (POF4-217) / 5111 - Domain-Specific Simulation
Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) /
Forschergruppe Gohlke $(hkf7_20200501)$ / DFG project
267205415 - SFB 1208: Identität und Dynamik von
Membransystemen - von Molekülen bis zu zellulären
Funktionen},
pid = {G:(DE-HGF)POF4-2171 / G:(DE-HGF)POF4-2172 /
G:(DE-HGF)POF4-5111 / $G:(DE-Juel1)hkf7_20200501$ /
G:(GEPRIS)267205415},
typ = {PUB:(DE-HGF)16},
pubmed = {34638686},
UT = {WOS:000708182600001},
doi = {10.3390/ijms221910345},
url = {https://juser.fz-juelich.de/record/901866},
}