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PDBsum entry 6mmt
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Transport protein
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PDB id
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6mmt
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References listed in PDB file
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Key reference
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Title
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Mechanisms for zinc and proton inhibition of the glun1/glun2a nmda receptor.
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Authors
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F.Jalali-Yazdi,
S.Chowdhury,
C.Yoshioka,
E.Gouaux.
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Ref.
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Cell, 2018,
175,
1520.
[DOI no: ]
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PubMed id
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Abstract
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N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory
formation, neuronal plasticity, and brain development, with their dysfunction
linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are
physiological allosteric modulators of NMDARs, with GluN2A-containing receptors
inhibited by nanomolar concentrations of divalent zinc and by excursions to low
pH. Despite the widespread importance of zinc and proton modulation of NMDARs,
the molecular mechanism by which these ions modulate receptor activity has
proven elusive. Here, we use cryoelectron microscopy to elucidate the structure
of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of
physiologically relevant zinc and proton concentrations. We show how zinc
binding to the amino terminal domain elicits structural changes that are
transduced though the ligand-binding domain and result in constriction of the
ion channel gate.
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