+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33229 | |||||||||
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Title | Cryo-EM structure of the galanin-bound GALR1-miniGo complex | |||||||||
Map data | cryoEM map of the GALR1/Go/galanin complex | |||||||||
Sample |
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Keywords | GPCR / Galanin receptor 1 / miniGo / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information galanin receptor binding / type 1 galanin receptor binding / type 2 galanin receptor binding / type 3 galanin receptor binding / guanyl nucleotide binding / galanin receptor activity / positive regulation of large conductance calcium-activated potassium channel activity / positive regulation of timing of catagen / positive regulation of cortisol secretion / regulation of glucocorticoid metabolic process ...galanin receptor binding / type 1 galanin receptor binding / type 2 galanin receptor binding / type 3 galanin receptor binding / guanyl nucleotide binding / galanin receptor activity / positive regulation of large conductance calcium-activated potassium channel activity / positive regulation of timing of catagen / positive regulation of cortisol secretion / regulation of glucocorticoid metabolic process / negative regulation of lymphocyte proliferation / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / negative regulation of adenylate cyclase activity / neuropeptide hormone activity / G protein-coupled peptide receptor activity / vesicle docking involved in exocytosis / feeding behavior / neuropeptide binding / insulin secretion / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / peptide hormone binding / response to immobilization stress / neuropeptide signaling pathway / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / muscle contraction / cAMP-mediated signaling / protein kinase A signaling / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / secretory granule / locomotory behavior / adenylate cyclase-activating G protein-coupled receptor signaling pathway / response to insulin / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / response to estrogen / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / 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 / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of apoptotic process / response to xenobiotic stimulus / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / neuronal cell body / dendrite / synapse / GTP binding / protein-containing complex binding / signal transduction Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Jiang W / Zheng S | |||||||||
Funding support | China, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Structural insights into galanin receptor signaling. Authors: Wentong Jiang / Sanduo Zheng / Abstract: Galanin is a biologically active neuropeptide, and functions through three distinct G protein–coupled receptors (GPCRs), namely GALR1, GALR2, and GALR3. GALR signaling plays important roles in ...Galanin is a biologically active neuropeptide, and functions through three distinct G protein–coupled receptors (GPCRs), namely GALR1, GALR2, and GALR3. GALR signaling plays important roles in regulating various physiological processes such as energy metabolism, neuropathic pain, epileptic activity, and sleep homeostasis. GALR1 and GALR3 signal through the Gi/o pathway, whereas GALR2 signals mainly through the Gq/11 pathway. However, the molecular basis for galanin recognition and G protein selectivity of GALRs remains poorly understood. Here, we report the cryoelectron microscopy structures of the GALR1-Go and the GALR2-Gq complexes bound to the endogenous ligand galanin or spexin. The galanin peptide mainly adopts an alpha helical structure, which binds at the extracellular vestibule of the receptors, nearly parallel to the membrane plane without penetrating deeply into the receptor core. Structural analysis combined with functional studies reveals important structural determinants for the G protein selectivity of GALRs as well as other class A GPCRs. In addition, we show that the zinc ion is a negative allosteric regulator of GALR1 but not GALR2. Our studies provide insight into the mechanisms of G protein selectivity of GPCRs and highlight a potential function of the neuromodulator zinc ion as a modulator of GPCR signaling in the central nervous system. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33229.map.gz | 20.9 MB | EMDB map data format | |
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Header (meta data) | emd-33229-v30.xml emd-33229.xml | 21.3 KB 21.3 KB | Display Display | EMDB header |
Images | emd_33229.png | 29.3 KB | ||
Others | emd_33229_half_map_1.map.gz emd_33229_half_map_2.map.gz | 20.6 MB 20.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33229 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33229 | HTTPS FTP |
-Validation report
Summary document | emd_33229_validation.pdf.gz | 771.5 KB | Display | EMDB validaton report |
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Full document | emd_33229_full_validation.pdf.gz | 771.1 KB | Display | |
Data in XML | emd_33229_validation.xml.gz | 10.2 KB | Display | |
Data in CIF | emd_33229_validation.cif.gz | 11.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33229 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33229 | HTTPS FTP |
-Related structure data
Related structure data | 7xjjMC 7xjkC 7xjlC 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_33229.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | cryoEM map of the GALR1/Go/galanin complex | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map of the GALR1/Go/galanin complex
File | emd_33229_half_map_1.map | ||||||||||||
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Annotation | half map of the GALR1/Go/galanin complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map of the GALR1/Go/galanin complex
File | emd_33229_half_map_2.map | ||||||||||||
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Annotation | half map of the GALR1/Go/galanin complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Galanin-bound Galanin receptor type 1 in complex with miniGalphao...
Entire | Name: Galanin-bound Galanin receptor type 1 in complex with miniGalphao, Gbeta/gamma subunit and a single-chain variable fragment (scFv16) |
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Components |
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-Supramolecule #1: Galanin-bound Galanin receptor type 1 in complex with miniGalphao...
Supramolecule | Name: Galanin-bound Galanin receptor type 1 in complex with miniGalphao, Gbeta/gamma subunit and a single-chain variable fragment (scFv16) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: G protein subunit alpha o1,Guanine nucleotide-binding protein G(o...
Macromolecule | Name: G protein subunit alpha o1,Guanine nucleotide-binding protein G(o) subunit alpha type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.447115 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHGGS GGSGGTTGIV ETHFTFKNLH FRLFDVGGQ RSERKKWIHC FEDVTAIIFC VDLSDYNRMH ESLMLFDSIC NNKFFIDTSI ILFLNKKDLF GEKIKKSPLT I CFPEYTGP ...String: MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHGGS GGSGGTTGIV ETHFTFKNLH FRLFDVGGQ RSERKKWIHC FEDVTAIIFC VDLSDYNRMH ESLMLFDSIC NNKFFIDTSI ILFLNKKDLF GEKIKKSPLT I CFPEYTGP NTYEDAAAYI QAQFESKNRS PNKEIYCHMT CATDTNNAQV IFDAVTDIII ANNLRGCGLY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(o) subunit alpha |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: Galanin
Macromolecule | Name: Galanin / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 3.161446 KDa |
Sequence | String: GWTLNSAGYL LGPHAVGNHR SFSDKNGLTS UniProtKB: Galanin peptides |
-Macromolecule #4: Galanin receptor type 1
Macromolecule | Name: Galanin receptor type 1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 38.38293 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DYKDDDDKGS MELAVGNLSE GNASWPEPPA PEPGPLFGIG VENFVTLVVF GLIFALGVLG NSLVITVLAR SKPGKPRSTT NLFILNLSI ADLAYLLFCI PFQATVYALP TWVLGAFICK FIHYFFTVSM LVSIFTLAAM SVDRYVAIVH SRRSSSLRVS R NALLGVGC ...String: DYKDDDDKGS MELAVGNLSE GNASWPEPPA PEPGPLFGIG VENFVTLVVF GLIFALGVLG NSLVITVLAR SKPGKPRSTT NLFILNLSI ADLAYLLFCI PFQATVYALP TWVLGAFICK FIHYFFTVSM LVSIFTLAAM SVDRYVAIVH SRRSSSLRVS R NALLGVGC IWALSIAMAS PVAYHQGLFH PRASNQTFCW EQWPDPRHKK AYVVCTFVFG YLLPLLLICF CYAKVLNHLH KK LKNMSKK SEASKKKTAQ TVLVVVVVFG ISWLPHHIIH LWAEFGVFPL TPASFLFRIT AHCLAYSNSS VNPIIYAFLS ENF RKAYKQ VFKCHIGGGG GGAGALEVLF Q UniProtKB: Galanin receptor type 1 |
-Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.845078 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #6: single Fab chain (svFv16)
Macromolecule | Name: single Fab chain (svFv16) / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 31.857369 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: PDVQLVESGG GLVQPGGSRK LSCSASGFAF SSFGMHWVRQ APEKGLEWVA YISSGSGTIY YADTVKGRFT ISRDDPKNTL FLQMTSLRS EDTAMYYCVR SIYYYGSSPF DFWGQGTTLT VSSGGGGSGG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...String: PDVQLVESGG GLVQPGGSRK LSCSASGFAF SSFGMHWVRQ APEKGLEWVA YISSGSGTIY YADTVKGRFT ISRDDPKNTL FLQMTSLRS EDTAMYYCVR SIYYYGSSPF DFWGQGTTLT VSSGGGGSGG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE LKAAAGAPLE VLFQGPGAWS HPQFEKGAED QVDPRLIDGK GAAHHHHHHH H |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5.1 mg/mL | ||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 101.325 kPa | ||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281.15 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 426045 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | PDB-7xjj: |