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- PDB-8hk5: C5aR1-Gi-C5a protein complex -

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Basic information

Entry
Database: PDB / ID: 8hk5
TitleC5aR1-Gi-C5a protein complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • C5a anaphylatoxin chemotactic receptor 1
  • Complement C5
KeywordsMEMBRANE PROTEIN / GPCR / C5aR1 / C5a / complement
Function / homology
Function and homology information


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 / complement activation, alternative 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 / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of neutrophil chemotaxis / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / chemokine activity / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / endopeptidase inhibitor activity / photoreceptor outer segment membrane / 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 / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / positive regulation of chemokine production / 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 / mRNA transcription by RNA polymerase II / microglial cell activation / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / negative regulation of insulin secretion / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / cognition / positive regulation of angiogenesis / chemotaxis / ADP signalling through P2Y purinoceptor 12 / 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 / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / cell body / GTPase binding / midbody / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events / basolateral plasma membrane / phospholipase C-activating G protein-coupled receptor signaling pathway
Similarity search - Function
Anaphylatoxin chemotactic receptor, C3a/C5a1/C5a2 / : / Complement component 5, CUB domain / Formyl peptide receptor-related / Complement C3/4/5, macroglobulin domain MG1 / Macroglobulin domain MG1 / Anaphylatoxin, complement system domain / Anaphylatoxin domain signature. / Anaphylatoxin, complement system / Anaphylatoxin/fibulin ...Anaphylatoxin chemotactic receptor, C3a/C5a1/C5a2 / : / Complement component 5, CUB domain / Formyl peptide receptor-related / Complement C3/4/5, macroglobulin domain MG1 / Macroglobulin domain MG1 / Anaphylatoxin, complement system domain / Anaphylatoxin domain signature. / Anaphylatoxin, complement system / Anaphylatoxin/fibulin / Anaphylotoxin-like domain / Anaphylatoxin domain profile. / Anaphylatoxin homologous domain / Netrin C-terminal Domain / Netrin module, non-TIMP type / UNC-6/NTR/C345C module / Macroglobulin domain MG4 / Macroglobulin domain MG4 / Netrin domain / NTR domain profile. / Alpha-macroglobulin, receptor-binding / Alpha-macroglobulin, receptor-binding domain superfamily / Macroglobulin domain MG3 / : / A-macroglobulin receptor binding domain / Macroglobulin domain MG3 / A-macroglobulin receptor / Tissue inhibitor of metalloproteinases-like, OB-fold / Alpha-2-macroglobulin / Macroglobulin domain / Alpha-2-macroglobulin, bait region domain / Alpha-macroglobulin-like, TED domain / Alpha-2-macroglobulin family / MG2 domain / A-macroglobulin TED domain / Alpha-2-macroglobulin bait region domain / Alpha-2-Macroglobulin / Alpha-2-macroglobulin family / Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid / Rhopdopsin 7-helix transmembrane proteins / Rhodopsin 7-helix transmembrane proteins / G-protein alpha subunit, group I / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Immunoglobulin-like fold / Up-down Bundle / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
PALMITIC ACID / Guanine nucleotide-binding protein subunit gamma / Complement C5 / C5a anaphylatoxin chemotactic receptor 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Rattus norvegicus (Norway rat)
Bos taurus (domestic cattle)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å
AuthorsWang, Y. / Liu, W. / Xu, Y. / Zhuang, Y. / Xu, H.E.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81902085 China
CitationJournal: Nat Chem Biol / Year: 2023
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
DepositionNov 24, 2022Deposition site: PDBJ / Processing site: RCSB
Revision 1.0May 10, 2023Provider: repository / Type: Initial release
Revision 1.1May 24, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 8, 2023Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Nov 20, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: C5a anaphylatoxin chemotactic receptor 1
B: Complement C5
C: Guanine nucleotide-binding protein G(i) subunit alpha-1
D: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein subunit gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)133,8367
Polymers133,3235
Non-polymers5132
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 2 types, 2 molecules AB

#1: Protein C5a anaphylatoxin chemotactic receptor 1


Mass: 39372.375 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: C5AR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P21730
#2: Protein Complement C5


Mass: 8288.676 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: C5 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P01031

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Guanine nucleotide-binding protein ... , 3 types, 3 molecules CDG

#3: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1


Mass: 40313.863 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1


Mass: 37915.496 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54311
#5: Protein Guanine nucleotide-binding protein subunit gamma


Mass: 7432.554 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A6J0WY55

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Non-polymers , 1 types, 2 molecules

#6: Chemical ChemComp-PLM / PALMITIC ACID


Mass: 256.424 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H32O2

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: C5aR1-Gi-C5a protein complex / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES
Molecular weightValue: 0.16 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: NONE
Particle selectionNum. of particles selected: 4236350
3D reconstructionResolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 406559 / Symmetry type: POINT

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