5FWX

Crystal structure of the AMPA receptor GluA2/A4 N-terminal domain heterodimer

Summary for 5FWX

• Entry DOI: 10.2210/pdb5fwx/pdb
• Descriptor: GLUTAMATE RECEPTOR 2, GLUTAMATE RECEPTOR 4, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transport protein
• Biological source: RATTUS NORVEGICUS (NORWAY RAT); More
• Total number of polymer chains: 4
• Total formula weight: 177605.45

Authors

Garcia-Nafria, J.,Herguedas, B.,Greger, I.H. (deposition date: 2016-02-21, release date: 2016-03-16, Last modification date: 2024-11-13)

Primary citation

Herguedas, B.,Garcia-Nafria, J.,Cais, O.,Fernandez-Leiro, R.,Krieger, J.,Ho, H.,Greger, I.H.
Structure and Organization of Heteromeric Ampa-Type Glutamate Receptors.
Science, 352:3873-, 2016

PubMed Abstract: AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling.

PubMed: 26966189
DOI: 10.1126/SCIENCE.AAD3873

Experimental method

X-RAY DIFFRACTION (2.5 Å)