% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Dmitrieva:1032107,
author = {Dmitrieva, Natalia and Gholami, Samira and Alleva, Claudia
and Carloni, Paolo and Alfonso-Prieto, Mercedes and Fahlke,
Christoph},
title = {{T}ransport mechanism of {D}go{T}, a bacterial homolog of
{SLC}17 organic anion transporters},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {FZJ-2024-06005},
year = {2024},
note = {We thank Drs Andre Bazzone, Bassam Haddad, Andrei
Kostritskii, PiersilvioLongo and Jan-Philipp Machtens for
helpful discussions and Meike Berndt forexcellent technical
support. This work was supported by the
DeutscheForschungsgemeinschaft (German Research Foundation)
to ChF (FA 301/15–2), PC (CA 973/27-2) and MAP (AL
2511/1-2) as part of Research Unit FOR2518, DynIon. The
authors gratefully acknowledge computing time on the
supercomputer JURECA at Forschungszentrum Jülich under
grants dgoth and vglut-pt.Open Access article as part of the
DEAL agreement with Wiley.},
abstract = {The solute carrier 17 (SLC17) family contains anion
transportersthat accumulate neurotransmitters in secretory
vesicles, removecarboxylated monosaccharides from lysosomes,
or extrude organicanions from the kidneys and liver.We
combined classical moleculardynamics simulations, Markov
state modeling and hybrid firstprinciples quantum
mechanical/classical mechanical (QM/MM)simulations with
experimental approaches to describe the transportmechanisms
of a model bacterial protein, the D-galactonatetransporter
DgoT, at atomic resolution. We found that protonationof D46
and E133 precedes galactonate binding and that
substratebinding induces closure of the extracellular gate,
with the conservedR47 coupling substrate binding to
transmembrane helixmovement. After isomerization to an
inward-facing conformation,deprotonation of E133 and
subsequent proton transfer from D46 toE133 opens the
intracellular gate and permits galactonate
dissociationeither in its unprotonated form or after proton
transferfrom E133. After release of the second proton, apo
DgoT returns tothe outward-facing conformation. Our results
provide a frameworkto understand how various SLC17 transport
functions with distincttransport stoichiometries can be
attained through subtle variationsin proton and substrate
binding/unbinding.},
cin = {IBI-1 / INM-9},
ddc = {570},
cid = {I:(DE-Juel1)IBI-1-20200312 / I:(DE-Juel1)INM-9-20140121},
pnm = {5243 - Information Processing in Distributed Systems
(POF4-524) / 5241 - Molecular Information Processing in
Cellular Systems (POF4-524) / DFG project
G:(GEPRIS)426950122 - FOR 5046: Integrative Analyse
epithelialer SLC26 Anionentransporter – von der
molekularen Struktur zur Pathophysiologie (426950122) / DFG
project G:(GEPRIS)291198853 - FOR 2518: Funktionale Dynamik
von Ionenkanälen und Transportern - DynIon - (291198853) /
DFG project G:(GEPRIS)329460521 - Protonentransfer und
Substraterkennung in SLC17-Transportern (329460521)},
pid = {G:(DE-HGF)POF4-5243 / G:(DE-HGF)POF4-5241 /
G:(GEPRIS)426950122 / G:(GEPRIS)291198853 /
G:(GEPRIS)329460521},
typ = {PUB:(DE-HGF)25},
url = {https://juser.fz-juelich.de/record/1032107},
}