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Open data
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Basic information
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| Title | Structure of EP141-C3aR-Go complex | |||||||||||||||
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Keywords | GPCR / SIGNALING PROTEIN | |||||||||||||||
| Function / homology | Function and homology informationcomplement component C3a receptor activity / complement component C5a receptor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / positive regulation of neutrophil chemotaxis / vesicle docking involved in exocytosis / blood circulation / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway ...complement component C3a receptor activity / complement component C5a receptor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / positive regulation of neutrophil chemotaxis / vesicle docking involved in exocytosis / blood circulation / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway / positive regulation of macrophage chemotaxis / regulation of heart contraction / parallel fiber to Purkinje cell synapse / positive regulation of vascular endothelial growth factor production / postsynaptic modulation of chemical synaptic transmission / Purinergic signaling in leishmaniasis infection / specific granule membrane / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / Peptide ligand-binding receptors / Regulation of Complement cascade / locomotory behavior / calcium-mediated signaling / negative regulation of insulin secretion / G protein-coupled receptor activity / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of angiogenesis / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / chemotaxis / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / cell body / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / postsynaptic membrane / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / inflammatory response / lysosomal membrane / GTPase activity / synapse / dendrite / Neutrophil degranulation / GTP binding / protein-containing complex binding / glutamatergic synapse / signal transduction / extracellular exosome Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||
Authors | Yadav MK / Yadav R / Maharana J / Sarma P / Banerjee R / Shukla AK / Gati C | |||||||||||||||
| Funding support | India, United Kingdom, 4 items
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Citation | Journal: Cell / Year: 2023Title: Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors. Authors: Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha ...Authors: Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha Mishra / Htet A Khant / Mohamed Chami / Trent M Woodruff / Ramanuj Banerjee / Arun K Shukla / Cornelius Gati / ![]() Abstract: The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological ...The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders. | |||||||||||||||
| History |
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_36001.map.gz | 85.1 MB | EMDB map data format | |
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| Header (meta data) | emd-36001-v30.xml emd-36001.xml | 21.7 KB 21.7 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_36001_fsc.xml | 9.5 KB | Display | FSC data file |
| Images | emd_36001.png | 104.1 KB | ||
| Filedesc metadata | emd-36001.cif.gz | 6.9 KB | ||
| Others | emd_36001_half_map_1.map.gz emd_36001_half_map_2.map.gz | 84.6 MB 84.6 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36001 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36001 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8j6dMC ![]() 8hptC ![]() 8hqcC ![]() 8i95C ![]() 8i97C ![]() 8i9aC ![]() 8i9lC ![]() 8i9sC ![]() 8ia2C ![]() 8jzzC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_36001.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #1
| File | emd_36001_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_36001_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : Structure of EP141-C3aR-Go complex
| Entire | Name: Structure of EP141-C3aR-Go complex |
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| Components |
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-Supramolecule #1: Structure of EP141-C3aR-Go complex
| Supramolecule | Name: Structure of EP141-C3aR-Go complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Guanine nucleotide-binding protein G(o) subunit alpha
| Macromolecule | Name: 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: 28.193939 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYDQ VLHEDETTNR MHESLMLFDS ICNNKFFIDT S IILFLNKK ...String: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYDQ VLHEDETTNR MHESLMLFDS ICNNKFFIDT S IILFLNKK DLFGEKIKKS PLTICFPEYT GPNTYEDAAA YIQAQFESKN RSPNKEIYCH MTCATDTNNA QVIFDAVTDI II ANNLRGC GLY UniProtKB: 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: 38.534062 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: C3a anaphylatoxin chemotactic receptor
| Macromolecule | Name: C3a anaphylatoxin chemotactic receptor / 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: 59.808422 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSASF SAETNSTDLL SQPWNEPPVI LSMVILSLT FLLGLPGNGL VLWVAGLKMQ RTVNTIWFLH LTLADLLCCL SLPFSLAHLA LQGQWPYGRF LCKLIPSIIV L NMFASVFL ...String: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSASF SAETNSTDLL SQPWNEPPVI LSMVILSLT FLLGLPGNGL VLWVAGLKMQ RTVNTIWFLH LTLADLLCCL SLPFSLAHLA LQGQWPYGRF LCKLIPSIIV L NMFASVFL LTAISLDRCL VVFKPIWCQN HRNVGMACSI CGCIWVVAFV MCIPVFVYRE IFTTDNHNRC GYKFGLSSSL DY PDFYGDP LENRSLENIV QPPGEMNDRL DPSSFQTNDH PWTVPTVFQP QTFQRPSADS LPRGSARLTS QNLYSNVFKP ADV VSPKIP SGFPIEDHET SPLDNSDAFL STHLKLFPSA SSNSFYESEL PQGFQDYYNL GQFTDDDQVP TPLVAITITR LVVG FLLPS VIMIACYSFI VFRMQRGRFA KSQSKTFRVA VVVVAVFLVC WTPYHIFGVL SLLTDPETPL GKTLMSWDHV CIALA SANS CFNPFLYALL GKDFRKKARQ SIQGILEAAF SEELTRSTHC PSNNVISERN STTV UniProtKB: C3a anaphylatoxin chemotactic receptor |
-Macromolecule #4: EP141 peptide agonist
| Macromolecule | Name: EP141 peptide agonist / 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: 1.825188 KDa |
| Sequence | String: WWGKKYRASK LGLAR |
-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: 7.861143 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #6: Antibody fragment - ScFv16
| Macromolecule | Name: Antibody fragment - ScFv16 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 26.466486 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL K |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS GLACIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm |
| Sample stage | Cooling holder cryogen: NITROGEN |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
India,
United Kingdom, 4 items
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Processing
FIELD EMISSION GUN
