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Structure paper

TitleElucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy.
Journal, issue, pagesScience, Vol. 353, Issue 6294, Page 83-86, Year 2016
Publish dateJul 1, 2016
AuthorsEdward C Twomey / Maria V Yelshanskaya / Robert A Grassucci / Joachim Frank / Alexander I Sobolevsky /
PubMed AbstractAMPA-subtype ionotropic glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and contribute to high cognitive processes such as learning and memory. In the brain, AMPAR trafficking, ...AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and contribute to high cognitive processes such as learning and memory. In the brain, AMPAR trafficking, gating, and pharmacology is tightly controlled by transmembrane AMPAR regulatory proteins (TARPs). Here, we used cryo-electron microscopy to elucidate the structural basis of AMPAR regulation by one of these auxiliary proteins, TARP γ2, or stargazin (STZ). Our structures illuminate the variable interaction stoichiometry of the AMPAR-TARP complex, with one or two TARP molecules binding one tetrameric AMPAR. Analysis of the AMPAR-STZ binding interfaces suggests that electrostatic interactions between the extracellular domains of AMPAR and STZ play an important role in modulating AMPAR function through contact surfaces that are conserved across AMPARs and TARPs. We propose a model explaining how TARPs stabilize the activated state of AMPARs and how the interactions between AMPARs and their auxiliary proteins control fast excitatory synaptic transmission.
External linksScience / PubMed:27365450 / PubMed Central
MethodsEM (single particle)
Resolution6.4 - 8.7 Å
Structure data

8229

5kbs

EMDB-8229, PDB-5kbs:
Cryo-EM structure of GluA2-0xSTZ at 8.7 Angstrom resolution
Method: EM (single particle) / Resolution: 8.7 Å

8230

5kbt

EMDB-8230, PDB-5kbt:
Cryo-EM structure of GluA2-1xSTZ complex at 6.4 Angstrom resolution
Method: EM (single particle) / Resolution: 6.4 Å

8231

5kbu

EMDB-8231, PDB-5kbu:
Cryo-EM structure of GluA2-2xSTZ complex at 7.8 Angstrom resolution
Method: EM (single particle) / Resolution: 7.8 Å

8232

5kbv

EMDB-8232, PDB-5kbv:
Cryo-EM structure of GluA2 bound to antagonist ZK200775 at 6.8 Angstrom resolution
Method: EM (single particle) / Resolution: 6.8 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

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • rattus norvegicus (Norway rat)
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN / Cryo-EM

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