8p3y | pdb_00008p3y

Homomeric GluA2 flip R/G-edited Q/R-edited F231A mutant in tandem with TARP gamma-2, desensitized conformation 3

spinqualitylabelsall models 8p3y, resolution 3.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8p3y is a 8 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.55Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca(2+)-impermeable, or GluA2-lacking and Ca(2+)-permeable(1). Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies(2), structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPgamma3 auxiliary subunits (GluA1/gamma3). The gating core of both resting and open-state GluA1/gamma3 closely resembles GluA2-containing receptors. However, the sequence-diverse N-terminal domains (NTDs) give rise to a highly mobile assembly, enabling domain swapping and subunit re-alignments in the ligand-binding domain tier that are pronounced in desensitized states. These transitions underlie the unique kinetic properties of GluA1. A GluA2 mutant (F231A) increasing NTD dynamics phenocopies this behaviour, and exhibits reduced synaptic responses, reflecting the anchoring function of the AMPAR NTD at the synapse. Together, this work underscores how the subunit-diverse NTDs determine subunit arrangement, gating properties and ultimately synaptic signalling efficiency among AMPAR subtypes. Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor.,Zhang D, Ivica J, Krieger JM, Ho H, Yamashita K, Stockwell I, Baradaran R, Cais O, Greger IH Nature. 2023 Sep;621(7980):877-882. doi: 10.1038/s41586-023-06528-0. Epub 2023 , Sep 13. PMID:37704721 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA