| Structural highlightsFunctionGRIA2_RAT Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
Fast excitatory neurotransmission in the mammalian central nervous system is largely carried out by AMPA-sensitive ionotropic glutamate receptors1. Localized within the postsynaptic density of glutamatergic spines, AMPA receptors are composed of heterotetrameric receptor assemblies associated with auxiliary subunits, the most common of which are transmembrane AMPA-receptor regulatory proteins (TARPs). The association of TARPs with AMPA receptors modulates the kinetics of receptor gating and pharmacology, as well as trafficking2. Here we report the cryo-EM structure of the homomeric GluA2 AMPA receptor saturated with TARP gamma2 subunits, showing how the TARPs are arranged with four-fold symmetry around the ion channel domain, making extensive interactions with the M1, M2 and M4 TM helices. Poised like partially opened 'hands' underneath the two-fold symmetric ligand binding domain (LBD) 'clamshells', one pair of TARPs are juxtaposed near the LBD dimer interface, while the other pair are near the LBD dimer-dimer interface. The extracellular 'domains' of TARP are positioned to not only modulate LBD 'clamshell' closure, but also affect conformational rearrangements of the LBD layer associated with receptor activation and desensitization, while the TARP transmembrane (TM) domains buttress the ion channel pore.
Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM.,Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E Nature. 2016 Jul 1. doi: 10.1038/nature18961. PMID:27368053[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See AlsoReferences
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- ↑ Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E. Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM. Nature. 2016 Jul 1. doi: 10.1038/nature18961. PMID:27368053 doi:http://dx.doi.org/10.1038/nature18961
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