TY  - JOUR
AU  - Kortzak, Daniel
AU  - Alleva, Claudia
AU  - Weyand, Ingo
AU  - Ewers, David
AU  - Zimmermann, Meike I
AU  - Franzen, Arne
AU  - Machtens, Jan‐Philipp
AU  - Fahlke, Christoph
TI  - Allosteric gate modulation confers K + coupling in glutamate transporters
JO  - The EMBO journal
VL  - 38
IS  - 19
SN  - 1460-2075
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - FZJ-2019-04644
SP  - e101468
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31506973
UR  - <Go to ISI:>//WOS:000486931900001
DO  - DOI:10.15252/embj.2019101468
UR  - https://juser.fz-juelich.de/record/865082
ER  -