+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27873 | ||||||||||||||||||
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Title | Cryo-EM structure of the VPAC1R-PACAP27-Gs complex | ||||||||||||||||||
Map data | Consensus map of VPAC1R-PACAP27-Gs complex, postprocessed, -25 B factor sharpening | ||||||||||||||||||
Sample |
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Keywords | membrane protein / drug discovery / G protein coupled receptor / signalling | ||||||||||||||||||
Function / homology | Function and homology information pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / NGF-independant TRKA activation / neuropeptide hormone activity / regulation of G protein-coupled receptor signaling pathway / G protein-coupled peptide receptor activity / insulin secretion / peptide hormone receptor binding ...pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / NGF-independant TRKA activation / neuropeptide hormone activity / regulation of G protein-coupled receptor signaling pathway / G protein-coupled peptide receptor activity / insulin secretion / peptide hormone receptor binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / PKA activation in glucagon signalling / peptide hormone binding / cAMP-mediated signaling / hair follicle placode formation / negative regulation of cell cycle / developmental growth / D1 dopamine receptor binding / neuropeptide signaling pathway / intracellular transport / positive regulation of protein kinase activity / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / female pregnancy / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / bone development / adenylate cyclase-modulating 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / platelet aggregation / cognition / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / neuron projection development / regulation of protein localization / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / sensory perception of smell / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / perikaryon / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / receptor complex / neuron projection / G protein-coupled receptor signaling pathway / lysosomal membrane / signaling receptor binding / GTPase activity / synapse Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.3 Å | ||||||||||||||||||
Authors | Piper SJ / Belousoff MJ / Danev R / Sexton P / Wootten D | ||||||||||||||||||
Funding support | Australia, United Kingdom, Japan, 5 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Understanding VPAC receptor family peptide binding and selectivity. Authors: Sarah J Piper / Giuseppe Deganutti / Jessica Lu / Peishen Zhao / Yi-Lynn Liang / Yao Lu / Madeleine M Fletcher / Mohammed Akhter Hossain / Arthur Christopoulos / Christopher A Reynolds / ...Authors: Sarah J Piper / Giuseppe Deganutti / Jessica Lu / Peishen Zhao / Yi-Lynn Liang / Yao Lu / Madeleine M Fletcher / Mohammed Akhter Hossain / Arthur Christopoulos / Christopher A Reynolds / Radostin Danev / Patrick M Sexton / Denise Wootten / Abstract: The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a ...The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a comprehensive understanding of peptide binding and selectivity among different subfamily receptors is lacking. Here, we determine structures of active, Gs-coupled, VIP-VPAC1R, PACAP27-VPAC1R, and PACAP27-PAC1R complexes. Cryo-EM structural analyses and molecular dynamics simulations (MDSs) reveal fewer stable interactions between VPAC1R and VIP than for PACAP27, more extensive dynamics of VIP interaction with extracellular loop 3, and receptor-dependent differences in interactions of conserved N-terminal peptide residues with the receptor core. MD of VIP modelled into PAC1R predicts more transient VIP-PAC1R interactions in the receptor core, compared to VIP-VPAC1R, which may underlie the selectivity of VIP for VPAC1R over PAC1R. Collectively, our work improves molecular understanding of peptide engagement with the PAC1R and VPAC1R that may benefit the development of novel selective agonists. | ||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27873.map.gz | 8.8 MB | EMDB map data format | |
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Header (meta data) | emd-27873-v30.xml emd-27873.xml | 31.9 KB 31.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27873_fsc.xml | 11.3 KB | Display | FSC data file |
Images | emd_27873.png | 77.7 KB | ||
Masks | emd_27873_msk_1.map | 125 MB | Mask map | |
Filedesc metadata | emd-27873.cif.gz | 7.1 KB | ||
Others | emd_27873_additional_1.map.gz emd_27873_additional_2.map.gz emd_27873_additional_3.map.gz emd_27873_additional_4.map.gz emd_27873_half_map_1.map.gz emd_27873_half_map_2.map.gz | 98.1 MB 11.4 MB 4.9 MB 60.3 MB 98.6 MB 98.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27873 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27873 | HTTPS FTP |
-Related structure data
Related structure data | 8e3yMC 8e3xC 8e3zC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27873.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Consensus map of VPAC1R-PACAP27-Gs complex, postprocessed, -25 B factor sharpening | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.65 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_27873_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Consensus map of VPAC1R-PACAP27-Gs complex, refinement map
File | emd_27873_additional_1.map | ||||||||||||
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Annotation | Consensus map of VPAC1R-PACAP27-Gs complex, refinement map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Consensus map of VPAC1R-PACAP27-Gs complex, postprocessed, auto B...
File | emd_27873_additional_2.map | ||||||||||||
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Annotation | Consensus map of VPAC1R-PACAP27-Gs complex, postprocessed, auto B factor sharpening | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Receptor-focused map of VPAC1R-PACAP27-Gs complex
File | emd_27873_additional_3.map | ||||||||||||
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Annotation | Receptor-focused map of VPAC1R-PACAP27-Gs complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: CryoSPARC non-uniform refinement map of VPAC1R-PACAP27-Gs complex
File | emd_27873_additional_4.map | ||||||||||||
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Annotation | CryoSPARC non-uniform refinement map of VPAC1R-PACAP27-Gs complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1 of consensus refinement of VPAC1R-PACAP27-Gs complex
File | emd_27873_half_map_1.map | ||||||||||||
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Annotation | Half map 1 of consensus refinement of VPAC1R-PACAP27-Gs complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 of consensus refinement of VPAC1R-PACAP27-Gs complex
File | emd_27873_half_map_2.map | ||||||||||||
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Annotation | Half map 2 of consensus refinement of VPAC1R-PACAP27-Gs complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Gs coupled Vasoactive intestinal polypeptide receptor 1 (VPAC1) c...
+Supramolecule #1: Gs coupled Vasoactive intestinal polypeptide receptor 1 (VPAC1) c...
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #3: Nanobody35
+Supramolecule #4: Pituitary adenylate cyclase activating polypeptide-27
+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: Pituitary adenylate cyclase-activating polypeptide
+Macromolecule #6: Vasoactive intestinal polypeptide receptor 1
+Macromolecule #7: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 7.9 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: COUNTING / Average electron dose: 69.7 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |