+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38218 | |||||||||
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Title | Human GPR34 -Gi complex bound to M1 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | GPCR / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information G protein-coupled purinergic nucleotide receptor activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels ...G protein-coupled purinergic nucleotide receptor activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / photoreceptor outer segment / 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 / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / cell body / G alpha (s) signalling events / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / dendrite / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.83 Å | |||||||||
Authors | Kawahara R / Shihoya W / Nureki O | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Structural basis for lysophosphatidylserine recognition by GPR34. Authors: Tamaki Izume / Ryo Kawahara / Akiharu Uwamizu / Luying Chen / Shun Yaginuma / Jumpei Omi / Hiroki Kawana / Fengjue Hou / Fumiya K Sano / Tatsuki Tanaka / Kazuhiro Kobayashi / Hiroyuki H ...Authors: Tamaki Izume / Ryo Kawahara / Akiharu Uwamizu / Luying Chen / Shun Yaginuma / Jumpei Omi / Hiroki Kawana / Fengjue Hou / Fumiya K Sano / Tatsuki Tanaka / Kazuhiro Kobayashi / Hiroyuki H Okamoto / Yoshiaki Kise / Tomohiko Ohwada / Junken Aoki / Wataru Shihoya / Osamu Nureki / Abstract: GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron ...GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-G complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38218.map.gz | 5 MB | EMDB map data format | |
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Header (meta data) | emd-38218-v30.xml emd-38218.xml | 22.4 KB 22.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_38218_fsc.xml | 5.9 KB | Display | FSC data file |
Images | emd_38218.png | 126.8 KB | ||
Masks | emd_38218_msk_1.map | 5.3 MB | Mask map | |
Filedesc metadata | emd-38218.cif.gz | 6.8 KB | ||
Others | emd_38218_half_map_1.map.gz emd_38218_half_map_2.map.gz | 4.9 MB 4.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38218 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38218 | HTTPS FTP |
-Validation report
Summary document | emd_38218_validation.pdf.gz | 719.4 KB | Display | EMDB validaton report |
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Full document | emd_38218_full_validation.pdf.gz | 719 KB | Display | |
Data in XML | emd_38218_validation.xml.gz | 9.7 KB | Display | |
Data in CIF | emd_38218_validation.cif.gz | 13.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38218 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38218 | HTTPS FTP |
-Related structure data
Related structure data | 8xbhMC 8xbeC 8xbgC 8xbiC 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_38218.map.gz / Format: CCP4 / Size: 5.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.291 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_38218_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_38218_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_38218_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human GPR34-Gi complex bound to M1
+Supramolecule #1: Human GPR34-Gi complex bound to M1
+Supramolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Supramolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #5: Probable G-protein coupled receptor 34
+Supramolecule #6: scFv16
+Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
+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: Probable G-protein coupled receptor 34
+Macromolecule #5: scFv16
+Macromolecule #6: (2~{S})-2-azanyl-3-[[(2~{R})-1-ethoxy-3-[3-[2-[(3-phenoxyphenyl)m...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 12 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (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: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |