The Three-dimensional Structure of an Ionotropic Glutamate Receptor Reveals a Dimer-of-dimers Assembly.
The ionotropic glutamate receptors (iGluRs) represent a major family of ion channels whose quaternary structure has not yet been defined. Here, we present the three-dimensional structure of a fully assembled iGluR, determined at approximately 20A resolution by electron microscopy. Analysis of negatively stained single-particle images reveals the presence of 2-fold, but not 4-fold, symmetry for these tetrameric channels, providing the first direct structural evidence for a dimer-of-dimers assembly. The receptor appears elongated, measuring approximately 170Ax140Ax110A, with the 2-fold symmetry centered on its longitudinal axis. The overall molecular shape and symmetry suggest an orientation relative to the membrane and permit the identification of a putative transmembrane domain. Internal cavities located along the longitudinal axis may represent components of the ion conduction pathway.
Tichelaar
Willem
W
Ion Channel Structure Group, Max Planck Institute for Medical Research, Jahnstr. 29, D-69120 Heidelberg, Germany.
Safferling
Markus
M
Keinänen
Kari
K
Stark
Holger
H
Madden
Dean R
DR
D019281:Dimerization; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011487:Protein Conformation; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D007473:Ion Channels; D017470:Receptors, Glutamate