+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26597 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | CryoEM structure of Go-coupled 5-HT5AR in complex with 5-CT | |||||||||
Map data | main map DEEP sharp | |||||||||
Sample |
| |||||||||
Function / homology | Function and homology information adenylate cyclase-inhibiting serotonin receptor signaling pathway / Serotonin receptors / serotonin binding / G protein-coupled serotonin receptor activity / postsynaptic specialization membrane / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hippocampus development / Olfactory Signaling Pathway / Activation of the phototransduction cascade ...adenylate cyclase-inhibiting serotonin receptor signaling pathway / Serotonin receptors / serotonin binding / G protein-coupled serotonin receptor activity / postsynaptic specialization membrane / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hippocampus 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 activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / response to estradiol / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / perikaryon / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.73 Å | |||||||||
Authors | Zhang S / Fay JF / Roth BL | |||||||||
Funding support | United States, 2 items
| |||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2022 Title: Inactive and active state structures template selective tools for the human 5-HT receptor. Authors: Shicheng Zhang / He Chen / Chengwei Zhang / Ying Yang / Petr Popov / Jing Liu / Brian E Krumm / Can Cao / Kuglae Kim / Yan Xiong / Vsevolod Katritch / Brian K Shoichet / Jian Jin / Jonathan ...Authors: Shicheng Zhang / He Chen / Chengwei Zhang / Ying Yang / Petr Popov / Jing Liu / Brian E Krumm / Can Cao / Kuglae Kim / Yan Xiong / Vsevolod Katritch / Brian K Shoichet / Jian Jin / Jonathan F Fay / Bryan L Roth / Abstract: Serotonin receptors are important targets for established therapeutics and drug development as they are expressed throughout the human body and play key roles in cell signaling. There are 12 ...Serotonin receptors are important targets for established therapeutics and drug development as they are expressed throughout the human body and play key roles in cell signaling. There are 12 serotonergic G protein-coupled receptor members encoded in the human genome, of which the 5-hydroxytryptamine (5-HT) receptor (5-HTR) is the least understood and lacks selective tool compounds. Here, we report four high-resolution (2.73-2.80 Å) structures of human 5-HTRs, including an inactive state structure bound to an antagonist AS2674723 by crystallization and active state structures bound to a partial agonist lisuride and two full agonists, 5-carboxamidotryptamine (5-CT) and methylergometrine, by cryo-EM. Leveraging the new structures, we developed a highly selective and potent antagonist for 5-HTR. Collectively, these findings both enhance our understanding of this enigmatic receptor and provide a roadmap for structure-based drug discovery for 5-HTR. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_26597.map.gz | 54.5 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-26597-v30.xml emd-26597.xml | 23.8 KB 23.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26597_fsc.xml | 13.8 KB | Display | FSC data file |
Images | emd_26597.png | 69.4 KB | ||
Masks | emd_26597_msk_1.map | 64 MB | Mask map | |
Others | emd_26597_additional_1.map.gz emd_26597_half_map_1.map.gz emd_26597_half_map_2.map.gz | 59.5 MB 59.4 MB 59.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26597 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26597 | HTTPS FTP |
-Validation report
Summary document | emd_26597_validation.pdf.gz | 678.7 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_26597_full_validation.pdf.gz | 678.2 KB | Display | |
Data in XML | emd_26597_validation.xml.gz | 18.3 KB | Display | |
Data in CIF | emd_26597_validation.cif.gz | 24.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26597 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26597 | HTTPS FTP |
-Related structure data
Related structure data | 7um5MC 7um4C 7um6C 7um7C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
EM raw data | EMPIAR-11033 (Title: cryoEM structure of Go-coupled 5-HT5A with agonist 5-CT Data size: 351.8 Data #1: Aligned multi-frame micrographs [micrographs - single frame]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_26597.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | main map DEEP sharp | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.91 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_26597_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: Bfactor Sharp Map
File | emd_26597_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Bfactor Sharp Map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map B
File | emd_26597_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map A
File | emd_26597_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : Go-coupled 5-HT5AR complex
+Supramolecule #1: Go-coupled 5-HT5AR complex
+Supramolecule #2: 5-hydroxytryptamine receptor 5A, miniGo protein, Guanine nucleoti...
+Supramolecule #3: Single-chain variable fragment scFv16
+Macromolecule #1: 5-hydroxytryptamine receptor 5A
+Macromolecule #2: miniGo protein
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Single-chain variable fragment scFv16
+Macromolecule #6: 3-(2-azanylethyl)-1H-indole-5-carboxamide
+Macromolecule #7: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 29.1 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.352 µm / Nominal defocus min: 0.2 µm |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |