[English] 日本語
![](img/lk-miru.gif)
- EMDB-7962: Open state GluA2 in complex with STZ and blocked by AgTx-636, aft... -
+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-7962 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Open state GluA2 in complex with STZ and blocked by AgTx-636, after micelle signal subtraction | |||||||||
![]() | TMD-directed refinement, micelle signal subtracted | |||||||||
![]() |
| |||||||||
Function / homology | ![]() LGI-ADAM interactions / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / Presynaptic depolarization and calcium channel opening / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Twomey EC / Yelshanskaya MV / Vassilevski AA / Sobolevsky AI | |||||||||
![]() | ![]() Title: Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors. Authors: Edward C Twomey / Maria V Yelshanskaya / Alexander A Vassilevski / Alexander I Sobolevsky / ![]() ![]() Abstract: AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic ...AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider toxin AgTx-636, the spider toxin analog NASPM, and the adamantane derivative IEM-1460. Our structures provide insights into the architecture of the blocker binding site and the mechanism of trapping, which are critical for development of small molecules that specifically target calcium-permeable AMPA receptors. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 10.7 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 14.8 KB 14.8 KB | Display Display | ![]() |
Images | ![]() | 284.3 KB | ||
Others | ![]() | 6.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6o9gMC ![]() 7959C ![]() 7960C ![]() 7961C ![]() 6dlzC ![]() 6dm0C ![]() 6dm1C ![]() 6dm2 M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | TMD-directed refinement, micelle signal subtracted | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Additional map: Full map, micelle signal subtracted
File | emd_7962_additional.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Full map, micelle signal subtracted | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Open state GluA2 in complex with STZ and blocked by AgTx-636, aft...
Entire | Name: Open state GluA2 in complex with STZ and blocked by AgTx-636, after micelle signal subtraction |
---|---|
Components |
|
-Supramolecule #1: Open state GluA2 in complex with STZ and blocked by AgTx-636, aft...
Supramolecule | Name: Open state GluA2 in complex with STZ and blocked by AgTx-636, after micelle signal subtraction type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: The full-map (non-TMD-directed) is included as a supplemental file |
---|---|
Source (natural) | Organism: ![]() ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit
Macromolecule | Name: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 115.178531 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: NSIQIGGLFP RGADQEYSAF RVGMVQFSTS EFRLTPHIDN LEVANSFAVT NAFCSQFSRG VYAIFGFYDK KSVNTITSFC GTLHVSFIT PSFPTDGTHP FVIQMRPDLK GALLSLIEYY QWDKFAYLYD SDRGLSTLQA VLDSAAEKKW QVTAINVGNI N NDKKDETY ...String: NSIQIGGLFP RGADQEYSAF RVGMVQFSTS EFRLTPHIDN LEVANSFAVT NAFCSQFSRG VYAIFGFYDK KSVNTITSFC GTLHVSFIT PSFPTDGTHP FVIQMRPDLK GALLSLIEYY QWDKFAYLYD SDRGLSTLQA VLDSAAEKKW QVTAINVGNI N NDKKDETY RSLFQDLELK KERRVILDCE RDKVNDIVDQ VITIGKHVKG YHYIIANLGF TDGDLLKIQF GGAEVSGFQI VD YDDSLVS KFIERWSTLE EKEYPGAHTA TIKYTSALTY DAVQVMTEAF RNLRKQRIEI SRRGNAGDCL ANPAVPWGQG VEI ERALKQ VQVEGLSGNI KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVLTED DTSGLEQKTV VVTTILESPY VMMK KNHEM LEGNERYEGY CVDLAAEIAK HCGFKYKLTI VGDGKYGARD ADTKIWNGMV GELVYGKADI AIAPLTITLV REEVI DFSK PFMSLGISIM IKKPQKSKPG VFSFLDPLAY EIWMCIVFAY IGVSVVLFLV SRFSPYEWHT EEFEDGRETQ SSESTN EFG IFNSLWFSLG AFMQQGCDIS PRSLSGRIVG GVWWFFTLII ISSYTANLAA FLTVERMVSP IESAEDLSKQ TEIAYGT LD SGSTKEFFRR SKIAVFDKMW TYMRSAEPSV FVRTTAEGVA RVRKSKGKYA YLLESTMNEY IEQRKPCDTM KVGGNLDS K GYGIATPKGS SLGTPVNLAV LKLSEQGVLD KLKNKWWYDK GECGAKDSGS KEKTSALSLS NVAGVFYILV GGLGLAMLV ALIEFCYKSR AEAKRMKGTG LFDRGVQMLL TTVGAFAAFS LMTIAVGTDY WLYSRGVCKT KSVSEDETSK KNEEVMTHSG LWRTCCLEG NFKGLCKQID HFPEDADYEA DTAEYFLRAV RASSIFPILS VILLFMGGLC IAASEFYKTR HNIILSAGIF F VSAGLSNI IGIIVYISAN AGDPSKSDSK KNSYSYGWSF YFGALSFIIA EMVGVLAVHM FIDRHKQLTG GAE |
-Macromolecule #2: GLUTAMIC ACID
Macromolecule | Name: GLUTAMIC ACID / type: ligand / ID: 2 / Number of copies: 4 / Formula: GLU |
---|---|
Molecular weight | Theoretical: 147.129 Da |
Chemical component information | ![]() ChemComp-GLU: |
-Macromolecule #3: CYCLOTHIAZIDE
Macromolecule | Name: CYCLOTHIAZIDE / type: ligand / ID: 3 / Number of copies: 4 / Formula: CYZ |
---|---|
Molecular weight | Theoretical: 389.878 Da |
Chemical component information | ![]() ChemComp-CYZ: |
-Macromolecule #4: N~1~-{5-[(3-{[3-(D-arginylamino)propyl]amino}propyl)amino]pentyl}...
Macromolecule | Name: N~1~-{5-[(3-{[3-(D-arginylamino)propyl]amino}propyl)amino]pentyl}-N~2~-[(2,4-dihydroxyphenyl)acetyl]-D-aspartamide type: ligand / ID: 4 / Number of copies: 1 / Formula: GYD |
---|---|
Molecular weight | Theoretical: 636.787 Da |
Chemical component information | ![]() ChemComp-GYD: |
-Experimental details
-Structure determination
Method | ![]() |
---|---|
![]() | ![]() |
Aggregation state | particle |
-
Sample preparation
Concentration | 4 mg/mL |
---|---|
Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
Details | Open state GluA2 in complex with STZ and blocked by AgTx-636, after micelle signal subtraction |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 8.0 sec. / Average electron dose: 55.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin |
---|---|
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic![]() Details: Resolution for full map (supplemental file) is 4.8 angstrom. Number images used: 82131 |
-Atomic model buiding 1
Refinement | Space: REAL |
---|---|
Output model | ![]() PDB-6o9g: |