Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Modulation of GluA2-γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 30, Issue 10, Page 1481-1494, Year 2023
Publish date	Aug 31, 2023
Authors	Shanti Pal Gangwar / Laura Y Yen / Maria V Yelshanskaya / Aryeh Korman / Drew R Jones / Alexander I Sobolevsky /
PubMed Abstract	Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat ...Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron microscopy structures of rat GluA2 AMPAR complexes with inhibitory mouse γ5 and potentiating human cornichon-2 (CNIH2) auxiliary subunits. CNIH2 appears to destabilize the desensitized state of the complex by reducing the separation of the upper lobes in ligand-binding domain dimers. At the same time, CNIH2 stabilizes binding of polyamine spermidine to the selectivity filter of the closed ion channel. Nevertheless, CNIH2, and to a lesser extent γ5, attenuate polyamine block of the open channel and reduce the potency of the antiepileptic drug perampanel that inhibits the synaptic complex allosterically by binding to sites in the ion channel extracellular collar. These findings illustrate the fine-tuning of synaptic complex structure and function in an auxiliary subunit-dependent manner, which is critical for the study of brain region-specific neurotransmission and design of therapeutics for disease treatment.
External links	Nat Struct Mol Biol / PubMed:37653241 / PubMed Central
Methods	EM (single particle)
Resolution	2.72 - 3.88 Å
Structure data	16052 8bhf EMDB-16052, PDB-8bhf: Cryo-EM structure of stalled rabbit 80S ribosomes in complex with human CCR4-NOT and CNOT4 Method: EM (single particle) / Resolution: 3.1 Å 40741 8ss2 EMDB-40741, PDB-8ss2: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK and channel blocker spermidine (closed state) Method: EM (single particle) / Resolution: 3.58 Å 40742 8ss3 EMDB-40742, PDB-8ss3: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK and channel blocker spermidine (closed state) Method: EM (single particle) / Resolution: 3.21 Å 40743 8ss4 EMDB-40743, PDB-8ss4: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunits TARP gamma-5 and cornichon-2 (apo state) Method: EM (single particle) / Resolution: 3.3 Å 40744 8ss5 EMDB-40744, PDB-8ss5: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunit TARP gamma-5 (apo state) Method: EM (single particle) / Resolution: 3.56 Å 40745 8ss6 EMDB-40745, PDB-8ss6: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK, channel blocker spermidine and antiepileptic drug perampanel (closed state) Method: EM (single particle) / Resolution: 3.01 Å 40746 8ss7 EMDB-40746, PDB-8ss7: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK, channel blocker spermidine and antiepileptic drug perampanel (closed state) Method: EM (single particle) / Resolution: 2.76 Å 40747 8ss8 EMDB-40747, PDB-8ss8: Structure of AMPA receptor GluA2 complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) Method: EM (single particle) / Resolution: 2.81 Å 40748 8ss9 EMDB-40748, PDB-8ss9: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) Method: EM (single particle) / Resolution: 2.72 Å 40749 8ssa EMDB-40749, PDB-8ssa: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to glutamate and channel blocker spermidine (desensitized state) Method: EM (single particle) / Resolution: 3.88 Å 40750 8ssb EMDB-40750, PDB-8ssb: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to glutamate and channel blocker spermidine (desensitized state) Method: EM (single particle) / Resolution: 3.66 Å
Chemicals	ChemComp-MG: Unknown entry ChemComp-ZN: Unknown entry ChemComp-ZK1: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid / antagonist, medicationYM / Fanapanel ChemComp-PCW: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / DOPC, phospholipidYM ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-AJP: Digitonin / detergentYM / Digitonin ChemComp-SPD: SPERMIDINE / Spermidine ChemComp-NA: Unknown entry ChemComp-6ZP: 2-(6'-oxo-1'-phenyl[1',6'-dihydro[2,3'-bipyridine]]-5'-yl)benzonitrile / medicationYM / Perampanel ChemComp-HOH: WATER / Water ChemComp-GLU: GLUTAMIC ACID / Glutamic acid
Source	oryctolagus cuniculus (rabbit) homo sapiens (human) rattus norvegicus (Norway rat)
Keywords	RIBOSOME / translational control / mRNA decay / deadenylation / ribosome stalling / human CCR4-NOT / MEMBRANE PROTEIN / AMPA receptor / spermidine / TARP gamma-5 / cornichon-2 / SIGNALING PROTEIN / neurotransmission / Ion-channel / perampanel