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Open data
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Basic information
Entry | Database: PDB / ID: 8hpt | ||||||
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Title | Structure of C5a-pep bound mouse C5aR1 in complex with Go | ||||||
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![]() | SIGNATLING PROTEIN/IMMUNE SYSTEM / GPCR / G protein / SIGNALING PROTEIN / SIGNATLING PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() complement component C5a binding / cell proliferation in hindbrain / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / Peptide ligand-binding receptors / Regulation of Complement cascade / response to peptidoglycan / G alpha (i) signalling events / complement receptor mediated signaling pathway ...complement component C5a binding / cell proliferation in hindbrain / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / Peptide ligand-binding receptors / Regulation of Complement cascade / response to peptidoglycan / G alpha (i) signalling events / complement receptor mediated signaling pathway / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / 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 / G protein-coupled serotonin receptor binding / Neutrophil degranulation / neutrophil chemotaxis / locomotory behavior / muscle contraction / positive regulation of epithelial cell proliferation / G protein-coupled receptor activity / astrocyte activation / microglial cell activation / G-protein beta/gamma-subunit complex binding / mRNA transcription by RNA polymerase II / Olfactory Signaling Pathway / 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 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / positive regulation of angiogenesis / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / apical part of cell / GTPase binding / 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 / cytoplasmic vesicle / G alpha (s) signalling events / G alpha (q) signalling events / basolateral plasma membrane / negative regulation of neuron apoptotic process / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / defense response to Gram-positive bacterium / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / GTP binding / cell surface Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.39 Å | ||||||
![]() | Saha, S. / Maharana, J. / Yadav, M.K. / Sarma, P. / Chami, M. / Banerjee, R. / Shukla, A.K. | ||||||
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. #1: ![]() Title: Structure of a GPCR-G protein in complex with a synthetic peptide agonist Authors: Saha, S. / Maharana, J. / Yadav, M.K. / Sarma, P. / Chami, M. / Banerjee, R. / Shukla, A.K. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 221.7 KB | Display | ![]() |
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PDB format | ![]() | 165.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 47.8 KB | Display | |
Data in CIF | ![]() | 70.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 34943MC ![]() 8hqcC ![]() 8i95C ![]() 8i97C ![]() 8i9aC ![]() 8i9lC ![]() 8i9sC ![]() 8ia2C ![]() 8j6dC ![]() 8jzzC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BCG
#3: Protein | Mass: 27024.762 Da / Num. of mol.: 1 / Mutation: G42D,E43N,A227D,G230D,I332A,V335I Source method: isolated from a genetically manipulated source Details: This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha (Uniprot ID: P09471) called the "mini G(o) alpha";The initial sequence in the provided sample sequence is the ...Details: This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha (Uniprot ID: P09471) called the "mini G(o) alpha";The initial sequence in the provided sample sequence is the expression tag: "MGHHHHHHENLYFQGT",This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha (Uniprot ID: P09471) called the "mini G(o) alpha";The initial sequence in the provided sample sequence is the expression tag: "MGHHHHHHENLYFQGT" Source: (gene. exp.) ![]() ![]() ![]() |
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#4: Protein | Mass: 37198.656 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The initial sequence present in the sample sequence and absent in the coordinates is the expression tag: "MHHHHHHGSSGS" Source: (gene. exp.) ![]() ![]() ![]() |
#5: Protein | Mass: 6160.126 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The missing residues in the coordinates are the regions which are disordered. Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Protein/peptide / Antibody , 3 types, 3 molecules ADH
#1: Protein | Mass: 44958.422 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The initial sequence in the sample sequence is the expression tag (absent in the coordinates): "MGKTIIALSYIFCLVFADYKDDDDAANFTPVNGSSGNQSVRLVTSSSLEVLFQGPGSDPIDNSSFEINYDHYGTMDPNIPADGIHLPKRQP" ...Details: The initial sequence in the sample sequence is the expression tag (absent in the coordinates): "MGKTIIALSYIFCLVFADYKDDDDAANFTPVNGSSGNQSVRLVTSSSLEVLFQGPGSDPIDNSSFEINYDHYGTMDPNIPADGIHLPKRQP" The residues missing in the coordinates as compared to the sample sequence are the residues with disorder. Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 869.148 Da / Num. of mol.: 1 / Source method: obtained synthetically Details: This is a chemically synthesized peptide derived from the C-terminus of human C5a. Source: (synth.) synthetic construct (others) |
#6: Antibody | Mass: 27340.482 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The residues absent in the coordinates are the regions which are disordered. Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 42 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
Image scans | Movie frames/image: 40 |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.39 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 380463 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
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