This title appears in the Scientific Report :
2020
Please use the identifier:
http://hdl.handle.net/2128/24965 in citations.
Please use the identifier: http://dx.doi.org/10.15252/embj.2019101468 in citations.
Allosteric gate modulation confers K + coupling in glutamate transporters
Allosteric gate modulation confers K + coupling in glutamate transporters
Excitatory amino acid transporters (EAAT s) mediate glial and neuronal glutamate uptake to terminate synaptic transmission and to ensure low resting glutamate concentrations. Effective glutamate uptake is achieved by cotransport with 3 Na+ and 1 H+, in exchange with 1 K+. The underlying principles o...
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Personal Name(s): | Kortzak, Daniel |
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Alleva, Claudia / Weyand, Ingo / Ewers, David / Zimmermann, Meike I / Franzen, Arne / Machtens, Jan‐Philipp / Fahlke, Christoph (Corresponding author) | |
Contributing Institute: |
JARA - HPC; JARA-HPC Zelluläre Biophysik; ICS-4 |
Published in: | The EMBO journal, 38 (2019) 19, S. e101468 |
Imprint: |
Hoboken, NJ [u.a.]
Wiley
2019
|
PubMed ID: |
31506973 |
DOI: |
10.15252/embj.2019101468 |
Document Type: |
Journal Article |
Research Program: |
MOLECULAR MODELLING OF BIFUNCTIONAL MEMBRANE TRANSPORT PROTEINS Multiscale simulations of voltage-gated sodium channel complexes and clusters Molecular dynamics of the SLC26 family of ion channels and transporters Mechanisms of Ca2+-activated Cl- channels and lipid scramblases of the TMEM16 family Functional Macromolecules and Complexes Molecular dynamics simulations of P2X receptors |
Link: |
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Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.15252/embj.2019101468 in citations.
Excitatory amino acid transporters (EAAT s) mediate glial and neuronal glutamate uptake to terminate synaptic transmission and to ensure low resting glutamate concentrations. Effective glutamate uptake is achieved by cotransport with 3 Na+ and 1 H+, in exchange with 1 K+. The underlying principles of this complex transport stoichiometry remain poorly understood. We use molecular dynamics simulations and electrophysiological experiments to elucidate how mammalian EAAT s harness K+ gradients, unlike their K+‐independent prokaryotic homologues. Glutamate transport is achieved via elevator‐like translocation of the transport domain. In EAAT s, glutamate‐free re‐translocation is prevented by an external gate remaining open until K+ binding closes and locks the gate. Prokaryotic GltPh contains the same K+‐binding site, but the gate can close without K+. Our study provides a comprehensive description of K+‐dependent glutamate transport and reveals a hitherto unknown allosteric coupling mechanism that permits adaptions of the transport stoichiometry without affecting ion or substrate binding. |