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Yorodumi- EMDB-24570: Substance P bound to active human neurokinin 1 receptor in comple... -
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Basic information
| Entry | Database: EMDB / ID: EMD-24570 | ||||||||||||||||||||||||||||||||||||
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| Title | Substance P bound to active human neurokinin 1 receptor in complex with miniGs399 | ||||||||||||||||||||||||||||||||||||
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Keywords | Substance P / G protein / GPCR / Neurokinin / Tachykinin / SIGNALING PROTEIN / SIGNALING PROTEIN-MEMBRANE PROTEIN complex | ||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationsubstance P receptor binding / substance P receptor activity / positive regulation of corticosterone secretion / tachykinin receptor activity / positive regulation of flagellated sperm motility / aggressive behavior / Tachykinin receptors bind tachykinins / sperm ejaculation / positive regulation of uterine smooth muscle contraction / insemination ...substance P receptor binding / substance P receptor activity / positive regulation of corticosterone secretion / tachykinin receptor activity / positive regulation of flagellated sperm motility / aggressive behavior / Tachykinin receptors bind tachykinins / sperm ejaculation / positive regulation of uterine smooth muscle contraction / insemination / positive regulation of synaptic transmission, cholinergic / detection of abiotic stimulus / operant conditioning / positive regulation of lymphocyte proliferation / tachykinin receptor signaling pathway / response to ozone / sperm head / positive regulation of action potential / response to auditory stimulus / positive regulation of acute inflammatory response / positive regulation of blood pressure / smooth muscle contraction involved in micturition / regulation of smooth muscle cell proliferation / positive regulation of vascular permeability / positive regulation of hormone secretion / positive regulation of ossification / regulation of smooth muscle cell migration / positive regulation of leukocyte migration / eating behavior / negative regulation of heart rate / response to pain / positive regulation of vasoconstriction / behavioral response to pain / angiotensin-mediated drinking behavior / associative learning / positive regulation of epithelial cell migration / PKA activation in glucagon signalling / response to electrical stimulus / developmental growth / hair follicle placode formation / neuropeptide signaling pathway / long-term memory / D1 dopamine receptor binding / sperm flagellum / neuronal dense core vesicle / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / response to hormone / positive regulation of stress fiber assembly / sperm midpiece / sensory perception of pain / cellular response to glucagon stimulus / regulation of insulin secretion / response to progesterone / adenylate cyclase activator activity / trans-Golgi network membrane / positive regulation of epithelial cell proliferation / positive regulation of synaptic transmission, GABAergic / response to nicotine / negative regulation of inflammatory response to antigenic stimulus / cellular response to nerve growth factor stimulus / bone development / regulation of blood pressure / platelet aggregation / G-protein beta/gamma-subunit complex binding / cognition / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / sensory perception of smell / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding Similarity search - Function | ||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) / ![]() | ||||||||||||||||||||||||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||||||||||||||||||||||||||
Authors | Harris JA / Faust B | ||||||||||||||||||||||||||||||||||||
| Funding support | United States, Australia, 11 items
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Citation | Journal: Nat Chem Biol / Year: 2022Title: Selective G protein signaling driven by substance P-neurokinin receptor dynamics. Authors: Julian A Harris / Bryan Faust / Arisbel B Gondin / Marc André Dämgen / Carl-Mikael Suomivuori / Nicholas A Veldhuis / Yifan Cheng / Ron O Dror / David M Thal / Aashish Manglik / ![]() Abstract: The neuropeptide substance P (SP) is important in pain and inflammation. SP activates the neurokinin-1 receptor (NK1R) to signal via G and G proteins. Neurokinin A also activates NK1R, but leads to ...The neuropeptide substance P (SP) is important in pain and inflammation. SP activates the neurokinin-1 receptor (NK1R) to signal via G and G proteins. Neurokinin A also activates NK1R, but leads to selective G signaling. How two stimuli yield distinct G protein signaling at the same G protein-coupled receptor remains unclear. We determined cryogenic-electron microscopy structures of active NK1R bound to SP or the G-biased peptide SP6-11. Peptide interactions deep within NK1R are critical for receptor activation. Conversely, interactions between SP and NK1R extracellular loops are required for potent G signaling but not G signaling. Molecular dynamics simulations showed that these superficial contacts restrict SP flexibility. SP6-11, which lacks these interactions, is dynamic while bound to NK1R. Structural dynamics of NK1R agonists therefore depend on interactions with the receptor extracellular loops and regulate G protein signaling selectivity. Similar interactions between other neuropeptides and their cognate receptors may tune intracellular signaling. | ||||||||||||||||||||||||||||||||||||
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Structure visualization
| Movie |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_24570.map.gz | 115.9 MB | EMDB map data format | |
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| Header (meta data) | emd-24570-v30.xml emd-24570.xml | 28.9 KB 28.9 KB | Display Display | EMDB header |
| Images | emd_24570.png | 50.3 KB | ||
| Filedesc metadata | emd-24570.cif.gz | 7.4 KB | ||
| Others | emd_24570_additional_1.map.gz emd_24570_half_map_1.map.gz emd_24570_half_map_2.map.gz | 116.1 MB 16.8 MB 16.8 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24570 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24570 | HTTPS FTP |
-Validation report
| Summary document | emd_24570_validation.pdf.gz | 713.2 KB | Display | EMDB validaton report |
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| Full document | emd_24570_full_validation.pdf.gz | 712.7 KB | Display | |
| Data in XML | emd_24570_validation.xml.gz | 14.1 KB | Display | |
| Data in CIF | emd_24570_validation.cif.gz | 16.7 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24570 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24570 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7rmhMC ![]() 7rmgC ![]() 7rmiC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | |
| EM raw data | EMPIAR-10786 (Title: Cryo electron microscopy final particle stacks of Substance P-Neurokinin Receptor G protein complexesData size: 170.8 Data #1: Particle stack and final .star file for SP-NK1R-miniGs399 reconstruction [picked particles - single frame - processed] Data #2: Particle stack and final .star file for SP6-11-NK1R-miniGsq70 reconstruction [picked particles - single frame - processed] Data #3: Particle stack and final .star file for SP-NK1R-miniGsq70 reconstruction [picked particles - single frame - processed]) |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_24570.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: #1
| File | emd_24570_additional_1.map | ||||||||||||
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-Half map: #1
| File | emd_24570_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_24570_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : Substance P bound to Neurokinin1 receptor-miniGs399 complex
+Supramolecule #1: Substance P bound to Neurokinin1 receptor-miniGs399 complex
+Supramolecule #2: Substance P
+Supramolecule #3: Substance-P receptor
+Supramolecule #4: miniGs399
+Supramolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1/...
+Supramolecule #6: Nanobody 35
+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: Substance-P receptor
+Macromolecule #6: Substance P
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 3670 / Average exposure time: 1.52 sec. / Average electron dose: 49.4 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi


Keywords
Homo sapiens (human)
Authors
United States,
Australia, 11 items
Citation
UCSF Chimera




































Z (Sec.)
Y (Row.)
X (Col.)













































Trichoplusia ni (cabbage looper)
Processing

