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Structure paper

TitleStructures of the AMPA receptor in complex with its auxiliary subunit cornichon.
Journal, issue, pagesScience, Vol. 366, Issue 6470, Page 1259-1263, Year 2019
Publish dateDec 6, 2019
AuthorsTerunaga Nakagawa /
PubMed AbstractIn the brain, AMPA-type glutamate receptors (AMPARs) form complexes with their auxiliary subunits and mediate the majority of fast excitatory neurotransmission. Signals transduced by these complexes ...In the brain, AMPA-type glutamate receptors (AMPARs) form complexes with their auxiliary subunits and mediate the majority of fast excitatory neurotransmission. Signals transduced by these complexes are critical for synaptic plasticity, learning, and memory. The two major categories of AMPAR auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs); these subunits share little homology and play distinct roles in controlling ion channel gating and trafficking of AMPAR. Here, I report high-resolution cryo-electron microscopy structures of AMPAR in complex with CNIH3. Contrary to its predicted membrane topology, CNIH3 lacks an extracellular domain and instead contains four membrane-spanning helices. The protein-protein interaction interface that dictates channel modulation and the lipids surrounding the complex are revealed. These structures provide insights into the molecular mechanism for ion channel modulation and assembly of AMPAR/CNIH3 complexes.
External linksScience / PubMed:31806817
MethodsEM (single particle)
Resolution2.97 - 4.4 Å
Structure data

20330

6peq

EMDB-20330, PDB-6peq:
GluA2 in complex with its auxiliary subunit CNIH3 - map LBD-TMD-C3 - with antagonist ZK200775 -without NTD
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-20332:
GluA2 full length in complex with its auxiliary subunit CNIH3 in PS - with antagonist ZK200775
Method: EM (single particle) / Resolution: 4.4 Å

20654

6u5s

EMDB-20654, PDB-6u5s:
NTD of GluA2 in complex with CNIH3 - with antagonist ZK200775 - in pseudo-symmetric global conformation
Method: EM (single particle) / Resolution: 3.07 Å

20666

6u6i

EMDB-20666, PDB-6u6i:
NTD of GluA2 in complex with CNIH3 - with antagonist ZK200775 - in asymmetric global conformation
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-20717:
GluA2 in complex with complex full-length in AS, bound to antagonist ZK200775
Method: EM (single particle) / Resolution: 4.4 Å

20727

6ucb

EMDB-20727, PDB-6ucb:
GluA2 in complex with its auxiliary subunit CNIH3 - with antagonist ZK200775, LBD, TMD, CNIH3, and lipids
Method: EM (single particle) / Resolution: 3.28 Å

EMDB-20732:
GluA2 in complex with its auxiliary subunit CNIH3 in AS map I - (LBD-TMD-C3(AS) I) - with antagonist ZK200775, without NTD
Method: EM (single particle) / Resolution: 3.5 Å

20733

6ud4

EMDB-20733, PDB-6ud4:
GluA2 in complex with its auxiliary subunit CNIH3 in AS map II - (LBD-TMD-C3(AS) II)- with antagonist ZK200775, without NTD
Method: EM (single particle) / Resolution: 3.3 Å

20734

6ud8

EMDB-20734, PDB-6ud8:
GluA2 in complex with its auxiliary subunit CNIH3 - with antagonist ZK200775
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-ZK1:
{[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid / antagonist, medication*YM / Fanapanel

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

ChemComp-PAM:
PALMITOLEIC ACID / Palmitoleic acid

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • rattus norvegicus (Norway rat)
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN / ionotropic glutamate receptor / AMPA receptor / cornichon / auxiliary subunit / ion channel / ligand gated ion channel / synaptic transmission / excitatory synaptic transmission / neurotransmitter receptor / stargazin / TARP / ZK200775 / lipid / MPQX

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