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Structure paper

TitleNative AMPA receptor architecture reveals SynDIG4 engagement and auxiliary subunit heterogeneity.
Journal, issue, pagesSci Adv, Vol. 12, Issue 24, Page eaee7973, Year 2026
Publish dateJun 12, 2026
AuthorsChengli Fang / Eric Gouaux /
PubMed AbstractAMPA-type glutamate receptors (AMPARs) are complex assemblies whose compositional heterogeneity underlies diverse excitatory signaling in the mammalian brain. Here, we determine high-resolution cryo- ...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.
External linksSci Adv / PubMed:42284406 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.75 Å
Structure data

74377

9zkm

EMDB-74377, PDB-9zkm:
The LBD-TMD structure of native mouse AMPAR with 4 TARPs
Method: EM (single particle) / Resolution: 3.13 Å

74378

9zkn

EMDB-74378, PDB-9zkn:
The TMD structure of native mouse AMPAR with 4 TARPs
Method: EM (single particle) / Resolution: 2.8 Å

74379

9zko

EMDB-74379, PDB-9zko:
The LBD-TMD structure of native mouse AMPAR with 2 TARPs 2 CNIHs
Method: EM (single particle) / Resolution: 3.04 Å

74380

9zkp

EMDB-74380, PDB-9zkp:
The TMD structure of native mouse AMPAR with 2 TARPs 2 CNIHs
Method: EM (single particle) / Resolution: 2.87 Å

74381

9zkq

EMDB-74381, PDB-9zkq:
The LBD-TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH
Method: EM (single particle) / Resolution: 3.36 Å

74382

9zkr

EMDB-74382, PDB-9zkr:
The TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH
Method: EM (single particle) / Resolution: 3.08 Å

74383

9zks

EMDB-74383, PDB-9zks:
The LBD-TMD structure of native mouse AMPAR with 2 TARPs 2 CNIHs and PRRT1/SynDIG4
Method: EM (single particle) / Resolution: 3.36 Å

74384

9zkt

EMDB-74384, PDB-9zkt:
The TMD structure of native mouse AMPAR with 2 TARPs 2 CNIHs and PRRT1/SynDIG4
Method: EM (single particle) / Resolution: 3.04 Å

74385

9zku

EMDB-74385, PDB-9zku:
The LBD-TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH and PRRT1/SynDIG4
Method: EM (single particle) / Resolution: 3.75 Å

74386

9zkv

EMDB-74386, PDB-9zkv:
The LBD-TMD structure of native mouse AMPAR with 2 TARPs
Method: EM (single particle) / Resolution: 3.45 Å

74387

9zkw

EMDB-74387, PDB-9zkw:
The LBD-TMD structure of native mouse AMPAR with 3 TARPs
Method: EM (single particle) / Resolution: 3.33 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID

ChemComp-OLC:
(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

Source
  • mus musculus (house mouse)
KeywordsSIGNALING PROTEIN / iGluR / AMPA receptors

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