5KBV

Cryo-EM structure of GluA2 bound to antagonist ZK200775 at 6.8 Angstrom resolution

Summary for 5KBV

• Entry DOI: 10.2210/pdb5kbv/pdb
• Related: 5KBS 5KBT 5KBU
• EMDB information: 8229 8230 8231 8232
• Descriptor: Glutamate receptor 2, {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cryo-em, transport protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 371531.22

Authors

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.G.,Frank, J.,Sobolevsky, A.I. (deposition date: 2016-06-03, release date: 2016-07-13, Last modification date: 2024-11-20)

Primary citation

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I.
Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy.
Science, 353:83-86, 2016

PubMed Abstract: 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.

PubMed: 27365450
DOI: 10.1126/science.aaf8411

Experimental method

ELECTRON MICROSCOPY (6.8 Å)