9ZKT

The TMD structure of native mouse AMPAR with 2 TARPs 2 CNIHs and PRRT1/SynDIG4

Summary for 9ZKT

• Entry DOI: 10.2210/pdb9zkt/pdb
• EMDB information: 74384
• Descriptor: Glutamate receptor 1, Glutamate receptor 2, Protein cornichon homolog 2, ... (8 entities in total)
• Functional Keywords: iglur, ampa receptors, signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 9
• Total formula weight: 378107.01

Authors

Fang, C.L.,Gouaux, E. (deposition date: 2025-12-07, release date: 2026-04-29, Last modification date: 2026-06-24)

Primary citation

Fang, C.,Gouaux, E.
Native AMPA receptor architecture reveals SynDIG4 engagement and auxiliary subunit heterogeneity.
Sci Adv, 12:eaee7973-eaee7973, 2026

PubMed Abstract: AMPA-type glutamate receptors (AMPARs) are complex assemblies whose compositional heterogeneity underlies diverse excitatory signaling in the mammalian brain. Here, we determine high-resolution cryo-electron microscopy (cryo-EM) structures of native AMPAR complexes rapidly purified from mouse brain. These structures capture receptors in physiologically relevant assemblies containing distinct combinations of transmembrane AMPA receptor regulatory protein (TARP) and cornichon homolog (CNIH) auxiliary subunits and reveal unambiguous density for the brain-specific protein SynDIG4. The resolved topology and interaction network of SynDIG4 show that it engages the receptor through a CNIH-dependent interface and occupies a position adjacent to structural elements of GluA1 implicated in trafficking and synaptic plasticity. The diversity of auxiliary stoichiometries observed across native complexes highlights a flexible organizational scheme through which AMPARs incorporate distinct regulatory partners. These findings illuminate the organization of native AMPAR assemblies and define the structural context for SynDIG4 function in the mammalian brain.

PubMed: 42284406
DOI: 10.1126/sciadv.aee7973

Experimental method

ELECTRON MICROSCOPY (3.04 Å)