9S3O

Cerebellar GluA2/4 NTD heterophilic tetramer interface (focused refinement)

Summary for 9S3O

• Entry DOI: 10.2210/pdb9s3o/pdb
• EMDB information: 54543
• Descriptor: Glutamate receptor 4, Glutamate receptor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: ampa ionotropic glutamate receptor, signaling protein
• Biological source: Sus scrofa (pig); More
• Total number of polymer chains: 2
• Total formula weight: 189524.04

Authors

Sengupta, N.,Scrutton, A.,Greger, I.H.,Krieger, J.M. (deposition date: 2025-07-24, release date: 2025-12-24)

Primary citation

Scrutton, A.M.,Sengupta, N.,Ivica, J.,Stockwell, I.,Peak-Chew, S.,Singh, B.,Suzuki, K.,Chang, V.T.,McLaughlin, S.H.,Krieger, J.M.,Aricescu, A.R.,Greger, I.H.
Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum.
Science, :eaeb3577-eaeb3577, 2025

PubMed Abstract: AMPA receptors (AMPARs) are multimodal transducers of glutamatergic signals throughout the brain. Their diversity is exemplified in the cerebellum; at afferent synapses, AMPARs mediate high-frequency excitation, whereas in Bergmann glia (BG) they support calcium transients that modulate synaptic transmission. This spectrum arises from different combinations of core subunits (GluA1-4), auxiliary proteins, and post-transcriptional modifications. Here, using mass-spectrometry, cryo-EM, and electrophysiology, we characterize major cerebellar AMPARs in pig: calcium-impermeable GluA2/A4 heteromers with four TARP subunits, mainly neuronal in origin, and BG-specific calcium-permeable GluA1/A4 heteromers containing two Type-2 TARPs. We also showed that GluA4 receptors consistently exhibit compact N-terminal domains that promote their synaptic delivery. Our study defines the organizational principles of mammalian cerebellar AMPAR complexes and reveals how different receptor subtypes support cell-type specific functions.

PubMed: 41379938
DOI: 10.1126/science.aeb3577

Experimental method

ELECTRON MICROSCOPY (3.9 Å)