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- EMDB-36755: Structure of human C5a-desArg bound human C5aR1 in complex with Go -
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Open data
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Basic information
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Title | Structure of human C5a-desArg bound human C5aR1 in complex with Go | ||||||||||||
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![]() | GPCR / Cell Signaling / Immune system / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | ![]() complement component C5a signaling pathway / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / response to peptidoglycan / Terminal pathway of complement / membrane attack complex / sensory perception of chemical stimulus / complement receptor mediated signaling pathway / Activation of C3 and C5 ...complement component C5a signaling pathway / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / response to peptidoglycan / Terminal pathway of complement / membrane attack complex / sensory perception of chemical stimulus / complement receptor mediated signaling pathway / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / complement activation, alternative pathway / chemokine activity / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / amyloid-beta clearance / : / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / positive regulation of vascular endothelial growth factor production / negative regulation of insulin secretion / cellular defense response / G protein-coupled serotonin receptor binding / positive regulation of chemokine production / Peptide ligand-binding receptors / neutrophil chemotaxis / secretory granule membrane / locomotory behavior / complement activation, classical pathway / Regulation of Complement cascade / muscle contraction / G protein-coupled receptor activity / positive regulation of epithelial cell proliferation / astrocyte activation / microglial cell activation / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / mRNA transcription by RNA polymerase II / 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) / cognition / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / 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 / positive regulation of angiogenesis / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / chemotaxis / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / apical part of cell / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / cell body / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / basolateral plasma membrane / killing of cells of another organism / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.31 Å | ||||||||||||
![]() | Yadav MK / Yadav R / Maharana J / Sarma P / Banerjee R / Shukla AK / Gati C | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 167.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.2 KB 23.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.9 KB | Display | ![]() |
Images | ![]() | 83.5 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
Others | ![]() ![]() | 165 MB 165 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 817.6 KB | Display | ![]() |
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Full document | ![]() | 817.2 KB | Display | |
Data in XML | ![]() | 20 KB | Display | |
Data in CIF | ![]() | 25.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8jzzMC ![]() 8i95C ![]() 8i97C ![]() 8i9aC ![]() 8i9lC ![]() 8i9sC ![]() 8ia2C ![]() 8j6dC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.92 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36755_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36755_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : human C5a-desArg bound human C5aR1 in complex with Go
Entire | Name: human C5a-desArg bound human C5aR1 in complex with Go |
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Components |
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-Supramolecule #1: human C5a-desArg bound human C5aR1 in complex with Go
Supramolecule | Name: human C5a-desArg bound human C5aR1 in complex with Go / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: human C5a-desArg bound human C5aR1 in complex with Go
Supramolecule | Name: human C5a-desArg bound human C5aR1 in complex with Go / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3, #5-#6 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: antibody
Supramolecule | Name: antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
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 #2: Guanine nucleotide-binding protein G(o) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(o) subunit alpha / type: protein_or_peptide / ID: 2 Details: This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha called the mini G(o) alpha Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 27.024762 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYNR MHESLMLFDS ICNNKFFIDT SIILFLNKKD L FGEKIKKS ...String: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYNR MHESLMLFDS ICNNKFFIDT SIILFLNKKD L FGEKIKKS PLTICFPEYT GPNTYEDAAA YIQAQFESKN RSPNKEIYCH MTCATDTNNA QVIFDAVTDI IIANNLRGCG LY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(o) subunit alpha |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
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 #4: Antibody fragment ScFv16
Macromolecule | Name: Antibody fragment ScFv16 / type: protein_or_peptide / ID: 4 / 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 |
-Macromolecule #5: C5a anaphylatoxin chemotactic receptor 1
Macromolecule | Name: C5a anaphylatoxin chemotactic receptor 1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 45.273867 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSDSF NYTTPDYGHY DDKDTLDLNT PVDKTSNTL RVPDILALVI FAVVFLVGVL GNALVVWVTA FEAKRTINAI WFLNLAVADF LSCLALPILF TSIVQHHHWP F GGAACSIL ...String: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSDSF NYTTPDYGHY DDKDTLDLNT PVDKTSNTL RVPDILALVI FAVVFLVGVL GNALVVWVTA FEAKRTINAI WFLNLAVADF LSCLALPILF TSIVQHHHWP F GGAACSIL PSLILLNMYA SILLLATISA DRFLLVFKPI WCQNFRGAGL AWIACAVAWG LALLLTIPSF LYRVVREEYF PP KVLCGVD YSHDKRRERA VAIVRLVLGF LWPLLTLTIC YTFILLRTWS RRATRSTKTL KVVVAVVASF FIFWLPYQVT GIM MSFLEP SSPTFLLLKK LDSLCVSFAY INCCINPIIY VVAGQGFQGR LRKSLPSLLR NVLTEESVVR ESKSFTRSTV DTMA QKTQA V UniProtKB: C5a anaphylatoxin chemotactic receptor 1 |
-Macromolecule #6: C5a anaphylatoxin
Macromolecule | Name: C5a anaphylatoxin / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 8.288676 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: TLQKKIEEIA AKYKHSVVKK CCYDGACVNN DETCEQRAAR ISLGPRCIKA FTECCVVASQ LRANISHKDM QLGR UniProtKB: Complement C5 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | 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: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm |