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Open data
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Basic information
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Title | C5aR1-Gi-C5a protein complex | |||||||||
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![]() | GPCR / C5aR1 / C5a / complement / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() complement component C5a signaling pathway / presynapse organization / complement component C5a receptor activity / Terminal pathway of complement / response to peptidoglycan / membrane attack complex / sensory perception of chemical stimulus / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement receptor mediated signaling pathway ...complement component C5a signaling pathway / presynapse organization / complement component C5a receptor activity / Terminal pathway of complement / response to peptidoglycan / membrane attack complex / sensory perception of chemical stimulus / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement receptor mediated signaling pathway / 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 / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / complement activation, alternative pathway / Vasopressin regulates renal water homeostasis via Aquaporins / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / chemokine activity / positive regulation of neutrophil chemotaxis / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / photoreceptor outer segment membrane / endopeptidase inhibitor activity / spectrin binding / positive regulation of macrophage chemotaxis / alkylglycerophosphoethanolamine phosphodiesterase activity / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / photoreceptor outer segment / complement activation, classical pathway / cellular defense response / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / positive regulation of chemokine production / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / photoreceptor inner segment / cardiac muscle cell apoptotic process / neutrophil chemotaxis / cellular response to forskolin / regulation of mitotic spindle organization / Peptide ligand-binding receptors / secretory granule membrane / positive regulation of epithelial cell proliferation / Regulation of Complement cascade / astrocyte activation / Regulation of insulin secretion / microglial cell activation / mRNA transcription by RNA polymerase II / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / G-protein beta/gamma-subunit complex binding / centriolar satellite / cognition / positive regulation of angiogenesis / ADP signalling through P2Y purinoceptor 12 / chemotaxis / Adrenaline,noradrenaline inhibits insulin secretion / GDP binding / G alpha (z) signalling events / ADORA2B mediated anti-inflammatory cytokines production / apical part of cell / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of taste / signaling receptor complex adaptor activity / G protein activity / cell body / GTPase binding / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / midbody / cell cortex / G alpha (i) signalling events / basolateral plasma membrane / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / cellular response to hypoxia Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Wang Y / Liu W / Xu Y / Zhuang Y / Xu HE | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Authors: Yue Wang / Weiyi Liu / Youwei Xu / Xinheng He / Qingning Yuan / Ping Luo / Wenjia Fan / Jingpeng Zhu / Xinyue Zhang / Xi Cheng / Yi Jiang / H Eric Xu / Youwen Zhuang / ![]() Abstract: The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations ...The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 51.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.7 KB 19.7 KB | Display Display | ![]() |
Images | ![]() | 33.2 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
Others | ![]() ![]() | 46.2 MB 46.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hk5MC ![]() 8hk2C ![]() 8hk3C C: citing same article ( M: atomic model generated by this map |
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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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_34846_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_34846_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : C5aR1-Gi-C5a protein complex
Entire | Name: C5aR1-Gi-C5a protein complex |
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Components |
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-Supramolecule #1: C5aR1-Gi-C5a protein complex
Supramolecule | Name: C5aR1-Gi-C5a protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 160 KDa |
-Macromolecule #1: C5a anaphylatoxin chemotactic receptor 1
Macromolecule | Name: C5a anaphylatoxin chemotactic receptor 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.372375 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MDSFNYTTPD YGHYDDKDTL DLNTPVDKTS NTLRVPDILA LVIFAVVFLV GVLGNALVVW VTAFEAKRTI NAIWFLNLAV ADFLSCLAL PILFTSIVQH HHWPFGGAAC SILPSLILLN MYASILLLAT ISADRFLLVF KPIWCQNFRG AGLAWIACAV A WGLALLLT ...String: MDSFNYTTPD YGHYDDKDTL DLNTPVDKTS NTLRVPDILA LVIFAVVFLV GVLGNALVVW VTAFEAKRTI NAIWFLNLAV ADFLSCLAL PILFTSIVQH HHWPFGGAAC SILPSLILLN MYASILLLAT ISADRFLLVF KPIWCQNFRG AGLAWIACAV A WGLALLLT IPSFLYRVVR EEYFPPKVLC GVDYSHDKRR ERAVAIVRLV LGFLWPLLTL TICYTFILLR TWSRRATRST KT LKVVVAV VASFFIFWLP YQVTGIMMSF LEPSSPTFLL LKKLDSLCVS FAYINCCINP IIYVVAGQGF QGRLRKSLPS LLR NVLTEE SVVRESKSFT RSTVDTMAQK TQAV UniProtKB: C5a anaphylatoxin chemotactic receptor 1 |
-Macromolecule #2: Complement C5
Macromolecule | Name: Complement C5 / type: protein_or_peptide / ID: 2 / 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 |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 40.313863 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GCTLSAEDKA AVERSKMIDR NLREDGEKAA REVKLLLLGA GESGKSTIVK QMKIIHEAGY SEEECKQYKA VVYSNTIQSI IAIIRAMGR LKIDFGDSAR ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND SAAYYLNDLD R IAQPNYIP ...String: GCTLSAEDKA AVERSKMIDR NLREDGEKAA REVKLLLLGA GESGKSTIVK QMKIIHEAGY SEEECKQYKA VVYSNTIQSI IAIIRAMGR LKIDFGDSAR ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND SAAYYLNDLD R IAQPNYIP TQQDVLRTRV KTTGIVETHF TFKDLHFKMF DVGAQRSERK KWIHCFEGVT AIIFCVALSD YDLVLAEDEE MN RMHESMK LFDSICNNKW FTDTSIILFL NKKDLFEEKI KKSPLTICYP EYAGSNTYEE AAAYIQCQFE DLNKRKDTKE IYT HFTCST DTKNVQFVFD AVTDVIIKNN LKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 37.915496 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #5: Guanine nucleotide-binding protein subunit gamma
Macromolecule | Name: Guanine nucleotide-binding protein subunit gamma / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.432554 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFC UniProtKB: Guanine nucleotide-binding protein subunit gamma |
-Macromolecule #6: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 6 / Number of copies: 2 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ![]() ChemComp-PLM: |
-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: 7.2 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |