The outer pore of the glutamate receptor channel has 2-fold rotational symmetry.
The ligand binding domain of glutamate receptors (GluRs) has 2-fold rotational symmetry. The structure including the symmetry of the GluR ion channel remains undefined. Here we used substituted cysteines in the pore-lining M3 segment of the AMPAR GluR-A subunit and various cysteine-reactive agents to study the structure of the channel during gating. We find that cysteines substituted at A+6, located in the highly conserved SYTANLAAF motif, are grouped in pairs consistent with a 2-fold symmetry in the extracellular part of the pore. To account for this symmetry and crosslinking, we propose that the M3 segments in two neighboring GluR subunits are kinked within SYTANLAAF in opposite directions relative to the central axis of the pore. Our results extend the 2-fold rotational symmetry from the ligand binding domain to at minimum the extracellular part of the channel and suggest a model of gating movements in GluR pore-forming domains.
Sobolevsky
Alexander I
AI
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794, USA. asobolevsky@notes2.cc.sunysb.edu
Yelshansky
Maria V
MV
Wollmuth
Lonnie P
LP
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D020816:Amino Acid Motifs / Q000502:physiology; D019943:Amino Acid Substitution / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002104:Cadmium / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D017124:Conserved Sequence / Q000502:physiology; D003300:Copper / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D008958:Models, Molecular; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D010618:Phenanthrolines / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000737:chemistry* / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D014494:Unithiol / Q000494:pharmacology; D014981:Xenopus
D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D010618:Phenanthrolines; D018091:Receptors, AMPA; D013438:Sulfhydryl Compounds; D002104:Cadmium; D018698:Glutamic Acid; D014494:Unithiol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003300:Copper; D003545:Cysteine; D004229:Dithiothreitol