+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30344 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the P395-bound GPBAR-Gs complex | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Function / homology | Function and homology information G protein-coupled bile acid receptor activity / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / positive regulation of cholangiocyte proliferation / : / cellular response to bile acid / Class A/1 (Rhodopsin-like receptors) / regulation of bicellular tight junction assembly / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth ...G protein-coupled bile acid receptor activity / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / positive regulation of cholangiocyte proliferation / : / cellular response to bile acid / Class A/1 (Rhodopsin-like receptors) / regulation of bicellular tight junction assembly / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / receptor complex / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Yang F / Mao C / Guo L / Lin J / Ming Q / Xiao P / Wu X / Shen Q / Guo S / Shen D ...Yang F / Mao C / Guo L / Lin J / Ming Q / Xiao P / Wu X / Shen Q / Guo S / Shen D / Lu R / Zhang L / Huang S / Ping Y / Zhang C / Ma C / Zhang K / Liang X / Shen Y / Nan F / Yi F / Luca V / Zhou J / Jiang C / Sun J / Xie X / Yu X / Zhang Y | |||||||||
Citation | Journal: Nature / Year: 2020 Title: Structural basis of GPBAR activation and bile acid recognition. Authors: Fan Yang / Chunyou Mao / Lulu Guo / Jingyu Lin / Qianqian Ming / Peng Xiao / Xiang Wu / Qingya Shen / Shimeng Guo / Dan-Dan Shen / Ruirui Lu / Linqi Zhang / Shenming Huang / Yuqi Ping / ...Authors: Fan Yang / Chunyou Mao / Lulu Guo / Jingyu Lin / Qianqian Ming / Peng Xiao / Xiang Wu / Qingya Shen / Shimeng Guo / Dan-Dan Shen / Ruirui Lu / Linqi Zhang / Shenming Huang / Yuqi Ping / Chenlu Zhang / Cheng Ma / Kai Zhang / Xiaoying Liang / Yuemao Shen / Fajun Nan / Fan Yi / Vincent C Luca / Jiuyao Zhou / Changtao Jiang / Jin-Peng Sun / Xin Xie / Xiao Yu / Yan Zhang / Abstract: The G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis. Here ...The G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis. Here we report the cryo-electron microscopy structures of GPBAR-G complexes stabilized by either the high-affinity P395 or the semisynthesized bile acid derivative INT-777 at 3 Å resolution. These structures revealed a large oval pocket that contains several polar groups positioned to accommodate the amphipathic cholic core of bile acids, a fingerprint of key residues to recognize diverse bile acids in the orthosteric site, a putative second bile acid-binding site with allosteric properties and structural features that contribute to bias properties. Moreover, GPBAR undertakes an atypical mode of activation and G protein coupling that features a different set of key residues connecting the ligand-binding pocket to the G-coupling site, and a specific interaction motif that is localized in intracellular loop 3. Overall, our study not only reveals unique structural features of GPBAR that are involved in bile acid recognition and allosteric effects, but also suggests the presence of distinct connecting mechanisms between the ligand-binding pocket and the G-protein-binding site in the G-protein-coupled receptor superfamily. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30344.map.gz | 17.9 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-30344-v30.xml emd-30344.xml | 21.2 KB 21.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30344_fsc.xml | 6.8 KB | Display | FSC data file |
Images | emd_30344.png | 74.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30344 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30344 | HTTPS FTP |
-Validation report
Summary document | emd_30344_validation.pdf.gz | 396 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_30344_full_validation.pdf.gz | 395.6 KB | Display | |
Data in XML | emd_30344_validation.xml.gz | 9.5 KB | Display | |
Data in CIF | emd_30344_validation.cif.gz | 12.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30344 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30344 | HTTPS FTP |
-Related structure data
Related structure data | 7cfmMC 7cfnC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_30344.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
+Entire : P395-bound GPBAR-Gs complex
+Supramolecule #1: P395-bound GPBAR-Gs complex
+Supramolecule #2: GPBAR
+Supramolecule #3: P395
+Supramolecule #4: Gs
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Nanobody-35
+Macromolecule #5: G-protein coupled bile acid receptor 1
+Macromolecule #6: 2-(ethylamino)-6-[3-(4-propan-2-ylphenyl)propanoyl]-7,8-dihydro-5...
+Macromolecule #7: CHOLESTEROL
+Macromolecule #8: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.0 mg/mL |
---|---|
Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 4826 / Average electron dose: 62.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 49310 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 29000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |