[English] 日本語
![](img/lk-miru.gif)
- EMDB-30323: Cryo-EM structure of human GABA(B) receptor bound to the positive... -
+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-30323 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of human GABA(B) receptor bound to the positive allosteric modulator rac-BHFF | |||||||||
![]() | active GABAB receptor | |||||||||
![]() |
| |||||||||
Function / homology | ![]() G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / GABA B receptor activation / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / G protein-coupled GABA receptor complex / negative regulation of gamma-aminobutyric acid secretion / neuron-glial cell signaling / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / negative regulation of epinephrine secretion / negative regulation of dopamine secretion ...G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / GABA B receptor activation / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / G protein-coupled GABA receptor complex / negative regulation of gamma-aminobutyric acid secretion / neuron-glial cell signaling / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / negative regulation of epinephrine secretion / negative regulation of dopamine secretion / positive regulation of growth hormone secretion / extracellular matrix protein binding / GABA receptor complex / negative regulation of adenylate cyclase activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / positive regulation of glutamate secretion / negative regulation of synaptic transmission / axolemma / GABA-ergic synapse / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / dendritic shaft / response to nicotine / Schaffer collateral - CA1 synapse / mitochondrial membrane / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / transmembrane signaling receptor activity / osteoblast differentiation / synaptic vesicle / presynaptic membrane / G alpha (i) signalling events / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / neuron projection / protein heterodimerization activity / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / neuronal cell body / glutamatergic synapse / endoplasmic reticulum membrane / extracellular space / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.5 Å | |||||||||
![]() | Kim Y / Jeong E / Jeong J / Cho Y | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Structural Basis for Activation of the Heterodimeric GABA Receptor. Authors: Yoojoong Kim / Eunyoung Jeong / Ji-Hong Jeong / Youngjin Kim / Yunje Cho / ![]() Abstract: The neurotransmitter γ-aminobutyric acid (GABA) activates the metabotropic GABA receptor to generate slow, prolonged inhibitory signals that regulate the neural circuitry. The GABA receptor is an ...The neurotransmitter γ-aminobutyric acid (GABA) activates the metabotropic GABA receptor to generate slow, prolonged inhibitory signals that regulate the neural circuitry. The GABA receptor is an obligate heterodimeric G protein-coupled receptor (GPCR) comprised of GBR1 and GBR2 subunits, each with extracellular, seven-helix transmembrane (7TM), and coiled-coil domains. To understand how GABA-driven conformational changes in the extracellular domain are transmitted to the 7TM domain during signal transduction, we determined cryo-electron microscopy (EM) structures of GABA in two different states: an antagonist-bound inactive state, and an active state in which both the GABA agonist and a positive allosteric modulator (PAM) are bound. In the inactive state, the TM3 and TM5 helices in the two 7TM domains engage in cholesterol-mediated as well as direct interactions, resulting in an open conformation. GABA binding forces the extracellular domains of GBR1 and GBR2 into a compact form, relocating the linkers that connect the extracellular and 7TM domains closer to each other. The movement of the linker along with the associated extracellular loop 2 of the 7TM domain reorients the two 7TM domains and creates a new interface with the TM5, TM6 and TM7 helices in a closed conformation. PAM binding to the interface between the TM6 and TM6 helices stabilizes the active 7TM domain conformation. The relayed structural rearrangement results in significant conformational changes in the TM helices, as well as intracellular loop 3 in GBR2, which may promote the binding and activation of the Gi/o proteins. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 95.6 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 13.4 KB 13.4 KB | Display Display | ![]() |
Images | ![]() | 39.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ca3MC ![]() 7ca5C ![]() 7cumC 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 | active GABAB receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
-Entire : Gamma-aminobutyric acid type B receptor
Entire | Name: Gamma-aminobutyric acid type B receptor |
---|---|
Components |
|
-Supramolecule #1: Gamma-aminobutyric acid type B receptor
Supramolecule | Name: Gamma-aminobutyric acid type B receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 / Details: Active Gamma-aminobutyric acid type B receptor |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Experimental: 200 kDa/nm |
-Macromolecule #1: Gamma-aminobutyric acid type B receptor subunit 1
Macromolecule | Name: Gamma-aminobutyric acid type B receptor subunit 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 87.248195 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRLLTALFAY FIVALILAFS VSAKSMSERR AVYIGALFPM SGGWPGGQAC QPAVEMALED VNSRRDILPD YELKLIHHDS KCDPGQATK YLYELLYNDP IKIILMPGCS SVSTLVAEAA RMWNLIVLSY GSSSPALSNR QRFPTFFRTH PSATLHNPTR V KLFEKWGW ...String: MRLLTALFAY FIVALILAFS VSAKSMSERR AVYIGALFPM SGGWPGGQAC QPAVEMALED VNSRRDILPD YELKLIHHDS KCDPGQATK YLYELLYNDP IKIILMPGCS SVSTLVAEAA RMWNLIVLSY GSSSPALSNR QRFPTFFRTH PSATLHNPTR V KLFEKWGW KKIATIQQTT EVFTSTLDDL EERVKEAGIE ITFRQSFFSD PAVPVKNLKR QDARIIVGLF YETEARKVFC EV YKERLFG KKYVWFLIGW YADNWFKIYD PSINCTVDEM TEAVEGHITT EIVMLNPANT RSISNMTSQE FVEKLTKRLK RHP EETGGF QEAPLAYDAI WALALALNKT SGGGGRSGVR LEDFNYNNQT ITDQIYRAMN SSSFEGVSGH VVFDASGSRM AWTL IEQLQ GGSYKKIGYY DSTKDDLSWS KTDKWIGGSP PADQTLVIKT FRFLSQKLFI SVSVLSSLGI VLAVVCLSFN IYNSH VRYI QNSQPNLNNL TAVGCSLALA AVFPLGLDGY HIGRNQFPFV CQARLWLLGL GFSLGYGSMF TKIWWVHTVF TKKEEK KEW RKTLEPWKLY ATVGLLVGMD VLTLAIWQIV DPLHRTIETF AKEEPKEDID VSILPQLEHC SSRKMNTWLG IFYGYKG LL LLLGIFLAYE TKSVSTEKIN DHRAVGMAIY NVAVLCLITA PVTMILSSQQ DAAFAFASLA IVFSSYITLV VLFVPKMR R LITRGEWQSE AQDTMKTGSS TNNNEEEKSR LLEKENRELE KSGRLEVLFQ |
-Macromolecule #2: Gamma-aminobutyric acid type B receptor subunit 2
Macromolecule | Name: Gamma-aminobutyric acid type B receptor subunit 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 92.231258 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG LMPLTKEVAK GSIGRGVLPA VELAIEQIR NESLLRPYFL DLRLYDTECD NAKGLKAFYD AIKYGPNHLM VFGGVCPSVT SIIAESLQGW NLVQLSFAAT T PVLADKKK ...String: MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG LMPLTKEVAK GSIGRGVLPA VELAIEQIR NESLLRPYFL DLRLYDTECD NAKGLKAFYD AIKYGPNHLM VFGGVCPSVT SIIAESLQGW NLVQLSFAAT T PVLADKKK YPYFFRTVPS DNAVNPAILK LLKHYQWKRV GTLTQDVQRF SEVRNDLTGV LYGEDIEISD TESFSNDPCT SV KKLKGND VRIILGQFDQ NMAAKVFCCA YEENMYGSKY QWIIPGWYEP SWWEQVHTEA NSSRCLRKNL LAAMEGYIGV DFE PLSSKQ IKTISGKTPQ QYEREYNNKR SGVGPSKFHG YAYDGIWVIA KTLQRAMETL HASSRHQRIQ DFNYTDHTLG RIIL NAMNE TNFFGVTGQV VFRNGERMGT IKFTQFQDSR EVKVGEYNAV ADTLEIINDT IRFQGSEPPK DKTIILEQLR KISLP LYSI LSALTILGMI MASAFLFFNI KNRNQKLIKM SSPYMNNLII LGGMLSYASI FLFGLDGSFV SEKTFETLCT VRTWIL TVG YTTAFGAMFA KTWRVHAIFK NVKMKKKIIK DQKLLVIVGG MLLIDLCILI CWQAVDPLRR TVEKYSMEPD PAGRDIS IR PLLEHCENTH MTIWLGIVYA YKGLLMLFGC FLAWETRNVS IPALNDSKYI GMSVYNVGIM CIIGAAVSFL TRDQPNVQ F CIVALVIIFC STITLCLVFV PKLITLRTNP DAATQNRRFQ FTQNQKKEDS KTSTSVTSVN QASTSRSGRG GSENLYFQG GSGSGGDYKD DDDKDYKDDD DK |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 3 / Formula: CLR |
---|---|
Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #4: (3S)-5,7-ditert-butyl-3-oxidanyl-3-(trifluoromethyl)-1-benzofuran...
Macromolecule | Name: (3S)-5,7-ditert-butyl-3-oxidanyl-3-(trifluoromethyl)-1-benzofuran-2-one type: ligand / ID: 4 / Number of copies: 1 / Formula: FN0 |
---|---|
Molecular weight | Theoretical: 330.342 Da |
Chemical component information | ![]() ChemComp-FN0: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 13 mg/mL |
---|---|
Buffer | pH: 7.5 |
Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 400 |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K3 (6k x 4k) / #0 - Average electron dose: 41.05 e/Å2 / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K3 (6k x 4k) / #1 - Average electron dose: 41.05 e/Å2 / #2 - Image recording ID: 3 / #2 - Film or detector model: GATAN K3 (6k x 4k) / #2 - Average electron dose: 41.05 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
-
Image processing
Image recording ID | 1 |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 294926 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |