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- EMDB-24570: Substance P bound to active human neurokinin 1 receptor in comple... -
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Open data
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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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Function / homology | ![]() substance P receptor binding / substance P receptor activity / insemination / tachykinin receptor activity / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / detection of abiotic stimulus / positive regulation of synaptic transmission, cholinergic ...substance P receptor binding / substance P receptor activity / insemination / tachykinin receptor activity / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / detection of abiotic stimulus / positive regulation of synaptic transmission, cholinergic / tachykinin receptor signaling pathway / positive regulation of lymphocyte proliferation / operant conditioning / sperm head / response to ozone / sperm ejaculation / positive regulation of action potential / response to auditory stimulus / smooth muscle contraction involved in micturition / regulation of smooth muscle cell proliferation / positive regulation of hormone secretion / positive regulation of blood pressure / positive regulation of vascular permeability / positive regulation of ossification / regulation of smooth muscle cell migration / positive regulation of leukocyte migration / eating behavior / response to pain / positive regulation of epithelial cell migration / behavioral response to pain / associative learning / PKA activation in glucagon signalling / angiotensin-mediated drinking behavior / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / sperm flagellum / neuropeptide signaling pathway / Hedgehog 'off' state / long-term memory / response to electrical stimulus / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / positive regulation of vasoconstriction / sensory perception of pain / sperm midpiece / positive regulation of stress fiber assembly / activation of adenylate cyclase activity / adenylate cyclase activator activity / cellular response to nerve growth factor stimulus / trans-Golgi network membrane / positive regulation of epithelial cell proliferation / response to progesterone / positive regulation of synaptic transmission, GABAergic / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / response to nicotine / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / cognition / 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 / platelet aggregation / 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 Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||||||||||||||||||||||||||
![]() | Harris JA / Faust B / Gondin AB / Daemgen MA / Suomivuori CM / Veldhuis NA / Cheng Y / Dror RO / Thal D / Manglik A | ||||||||||||||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: 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. | ||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 115.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.7 KB 29.7 KB | Display Display | ![]() |
Images | ![]() | 50.3 KB | ||
Others | ![]() ![]() ![]() | 116.1 MB 16.8 MB 16.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 619 KB | Display | ![]() |
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Full document | ![]() | 618.5 KB | Display | |
Data in XML | ![]() | 14.1 KB | Display | |
Data in CIF | ![]() | 16.6 KB | Display | |
Arichive directory | ![]() ![]() | 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 | ![]() Data 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 | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_24570_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_24570_half_map_2.map | ||||||||||||
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Projections & Slices |
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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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![]() | 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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |