+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33682 | |||||||||
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Title | Structure of the GPR17-Gi complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information : / Leukotriene receptors / P2Y receptors / chemokine receptor activity / receptor serine/threonine kinase binding / positive regulation of Rho protein signal transduction / oligodendrocyte differentiation / plasma membrane => GO:0005886 / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex ...: / Leukotriene receptors / P2Y receptors / chemokine receptor activity / receptor serine/threonine kinase binding / positive regulation of Rho protein signal transduction / oligodendrocyte differentiation / plasma membrane => GO:0005886 / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / negative regulation of inflammatory response to antigenic stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor activity / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating 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 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 / response to peptide hormone / 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 / GDP 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) / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / cell cycle / lysosomal membrane / cell division / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / human (human) / house mouse (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.02 Å | |||||||||
Authors | Ye F / Chen G | |||||||||
Funding support | 1 items
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Citation | Journal: MedComm (2020) / Year: 2022 Title: Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein. Authors: Fang Ye / Thian-Sze Wong / Geng Chen / Zhiyi Zhang / Binghao Zhang / Shiyi Gan / Wei Gao / Jiancheng Li / Zhangsong Wu / Xin Pan / Yang Du / Abstract: GPR17 is a class A orphan G protein-coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the ...GPR17 is a class A orphan G protein-coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the heterotrimeric Gi, but its activation mechanism is unclear. Here, we employed cryo-electron microscopy (cryo-EM) technology to elucidate the structure of activated GPR17-Gi complex. The 3.02 Å resolution structure, together with mutagenesis studies, revealed that the extracellular loop2 of GPR17 occupied the orthosteric binding pocket to promote its self-activation. The active GPR17 carried several typical microswitches like other class A GPCRs. Moreover, the Gi interacted with the key residues of transmembrane helix 3 (TM3), the amphipathic helix 8 (Helix8), and intracellular loops 3 (ICL3) in GPR17 to engage in the receptor core. In summary, our results highlight the activation mechanism of GPR17 from the structural basis. Elucidating the structural and activation mechanism of GPR17 may facilitate the pharmacological intervention for acute/chronic CNS injury. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33682.map.gz | 64.4 MB | EMDB map data format | |
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Header (meta data) | emd-33682-v30.xml emd-33682.xml | 16.9 KB 16.9 KB | Display Display | EMDB header |
Images | emd_33682.png | 103 KB | ||
Others | emd_33682_half_map_1.map.gz emd_33682_half_map_2.map.gz | 117.9 MB 117.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33682 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33682 | HTTPS FTP |
-Related structure data
Related structure data | 7y89MC 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_33682.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33682_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33682_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : GPR17-Gi
Entire | Name: GPR17-Gi |
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Components |
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-Supramolecule #1: GPR17-Gi
Supramolecule | Name: GPR17-Gi / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 40.153672 KDa |
Sequence | String: TLSAEDKAAV ERSKMIDRNL REDGEKAARE VKLLLLGAGE SGKSTIVKQM KIIHEAGYSE EECKQYKAVV YSNTIQSIIA IIRAMGRLK IDFGDSARAD DARQLFVLAG AAEEGFMTAE LAGVIKRLWK DSGVQACFNR SREYQLNDSA AYYLNDLDRI A QPNYIPTQ ...String: TLSAEDKAAV ERSKMIDRNL REDGEKAARE VKLLLLGAGE SGKSTIVKQM KIIHEAGYSE EECKQYKAVV YSNTIQSIIA IIRAMGRLK IDFGDSARAD DARQLFVLAG AAEEGFMTAE LAGVIKRLWK DSGVQACFNR SREYQLNDSA AYYLNDLDRI A QPNYIPTQ QDVLRTRVKT TGIVETHFTF KDLHFKMFDV GAQRSERKKW IHCFEGVTAI IFCVALSDYD LVLAEDEEMN RM HESMKLF DSICNNKWFT DTSIILFLNK KDLFEEKIKK SPLTICYPEY AGSNTYEEAA AYIQCQFEDL NKRKDTKEIY THF TCSTDT KNVQFVFDAV TDVIIKNNLK DCGLF |
-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: human (human) |
Molecular weight | Theoretical: 37.069543 KDa |
Sequence | String: LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVSA SQDGKLIIWD SYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH TGYLSCCRFL DDNQIVTSSG D TTCALWDI ...String: LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVSA SQDGKLIIWD SYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH TGYLSCCRFL DDNQIVTSSG D TTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FTGHESDINA ICFFPNGNAF AT GSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KADRAGVLAG HDNRVSCLGV TDD GMAVAT GSWDSFLKIW N |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 6.218162 KDa |
Sequence | String: SIAQARKLVE QLKMEANIDR IKVSKAAADL MAYCEAHAKE DPLLTPVPAS ENPFRE |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 26.424385 KDa |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE L |
-Macromolecule #5: Uracil nucleotide/cysteinyl leukotriene receptor
Macromolecule | Name: Uracil nucleotide/cysteinyl leukotriene receptor / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: house mouse (house mouse) |
Molecular weight | Theoretical: 33.067391 KDa |
Sequence | String: QCGQETPLEN MLFASFYLLD FILALVGNTL ALWLFIRDHK SGTPANVFLM HLAVADLSCV LVLPTRLVYH FSGNHWPFGE IACRLTGFL FYLNMYASIY FLTCISADRF LAIVHPVKSL KLRRPLYAHL ACAFLWVVVA VAMAPLLVSP QTVQTNHTVV C LQLYREKA ...String: QCGQETPLEN MLFASFYLLD FILALVGNTL ALWLFIRDHK SGTPANVFLM HLAVADLSCV LVLPTRLVYH FSGNHWPFGE IACRLTGFL FYLNMYASIY FLTCISADRF LAIVHPVKSL KLRRPLYAHL ACAFLWVVVA VAMAPLLVSP QTVQTNHTVV C LQLYREKA SHHALVSLAV AFTFPFITTV TCYLLIIRSL RQGLRVEKRL KTKAVRMIAI VLAIFLVCFV PYHVNRSVYV LH YRSHGAS CATQRILALA NRITSCLTSL NGALDPIMYF FVAEKFRHAL CNLLCG |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | cell |
-Sample preparation
Buffer | pH: 7.4 |
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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: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 57.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: OTHER |
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Final angle assignment | Type: OTHER |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 314674 |