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Open data
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Basic information
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| Title | Structure of a class A GPCR/agonist complex | |||||||||
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Keywords | GPCR / agonist / STRUCTURAL PROTEIN | |||||||||
| Function / homology | Function and homology informationchemokine receptor activity / CCR chemokine receptor binding / C-C chemokine receptor activity / chemokine-mediated signaling pathway / eosinophil chemotaxis / C-C chemokine binding / positive regulation of monocyte chemotaxis / chemokine activity / Chemokine receptors bind chemokines / positive regulation of interleukin-17 production ...chemokine receptor activity / CCR chemokine receptor binding / C-C chemokine receptor activity / chemokine-mediated signaling pathway / eosinophil chemotaxis / C-C chemokine binding / positive regulation of monocyte chemotaxis / chemokine activity / Chemokine receptors bind chemokines / positive regulation of interleukin-17 production / viral process / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / coreceptor activity / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / regulation of mitotic spindle organization / bioluminescence / cell chemotaxis / generation of precursor metabolites and energy / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / calcium-mediated signaling / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / intracellular calcium ion homeostasis / chemotaxis / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / positive regulation of inflammatory response / 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 / antimicrobial humoral immune response mediated by antimicrobial peptide / 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 / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / 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 / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / 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 / Extra-nuclear estrogen signaling / cell population proliferation / cell adhesion / immune response / ciliary basal body / positive regulation of cell migration Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() Human adenovirus C serotype 2 / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Sun D / Johnson M / Masureel M | |||||||||
| Funding support | 1 items
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Citation | Journal: Nat Commun / Year: 2023Title: Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8. Authors: Dawei Sun / Yonglian Sun / Eric Janezic / Tricia Zhou / Matthew Johnson / Caleigh Azumaya / Sigrid Noreng / Cecilia Chiu / Akiko Seki / Teresita L Arenzana / John M Nicoludis / Yongchang Shi ...Authors: Dawei Sun / Yonglian Sun / Eric Janezic / Tricia Zhou / Matthew Johnson / Caleigh Azumaya / Sigrid Noreng / Cecilia Chiu / Akiko Seki / Teresita L Arenzana / John M Nicoludis / Yongchang Shi / Baomei Wang / Hoangdung Ho / Prajakta Joshi / Christine Tam / Jian Payandeh / Laëtitia Comps-Agrar / Jianyong Wang / Sascha Rutz / James T Koerber / Matthieu Masureel / ![]() Abstract: The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an ...The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an attractive therapeutic approach, but the molecular basis for chemokine-mediated activation and antibody-mediated inhibition of CCR8 are not fully elucidated. Here, we obtain an antagonist antibody against human CCR8 and determine structures of CCR8 in complex with either the antibody or the endogenous agonist ligand CCL1. Our studies reveal characteristic antibody features allowing recognition of the CCR8 extracellular loops and CCL1-CCR8 interaction modes that are distinct from other chemokine receptor - ligand pairs. Informed by these structural insights, we demonstrate that CCL1 follows a two-step, two-site binding sequence to CCR8 and that antibody-mediated inhibition of CCL1 signaling can occur by preventing the second binding event. Together, our results provide a detailed structural and mechanistic framework of CCR8 activation and inhibition that expands our molecular understanding of chemokine - receptor interactions and offers insight into the development of therapeutic antibodies targeting chemokine GPCRs. | |||||||||
| History |
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_41829.map.gz | 43.5 MB | EMDB map data format | |
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| Header (meta data) | emd-41829-v30.xml emd-41829.xml | 17.2 KB 17.2 KB | Display Display | EMDB header |
| Images | emd_41829.png | 76.7 KB | ||
| Filedesc metadata | emd-41829.cif.gz | 6.9 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41829 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41829 | HTTPS FTP |
-Validation report
| Summary document | emd_41829_validation.pdf.gz | 478 KB | Display | EMDB validaton report |
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| Full document | emd_41829_full_validation.pdf.gz | 477.6 KB | Display | |
| Data in XML | emd_41829_validation.xml.gz | 6.6 KB | Display | |
| Data in CIF | emd_41829_validation.cif.gz | 7.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41829 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41829 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8u1uMC ![]() 8tlmC C: citing same article ( M: atomic model generated by this map |
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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_41829.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: 1.0153 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : CCR8 in complex with CCL1 and Gi
| Entire | Name: CCR8 in complex with CCL1 and Gi |
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| Components |
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-Supramolecule #1: CCR8 in complex with CCL1 and Gi
| Supramolecule | Name: CCR8 in complex with CCL1 and Gi / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: C-C motif chemokine 1,C-C chemokine receptor type 8,EGFP fusion p...
| Macromolecule | Name: C-C motif chemokine 1,C-C chemokine receptor type 8,EGFP fusion protein type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() Human adenovirus C serotype 2 |
| Molecular weight | Theoretical: 83.23668 KDa |
| Recombinant expression | Organism: Mammalian expression vector Flag-MCS-pcDNA3.1 (others) |
| Sequence | String: KSMQVPFSRC CFSFCEQEIP LRAILCYRNT SSICSNEGLI FKLKRGKEAC ALDTVGWVQR HRKMLRHCPS KRKGSGSGSG SGSGSGSGS GSGSGSGSDY TLDLSVTTVT DYYYPDICSS PCDAELIQTN GKLLLAVFYC LLFVFSLLGN SLVILVLVVC K KLRSITDV ...String: KSMQVPFSRC CFSFCEQEIP LRAILCYRNT SSICSNEGLI FKLKRGKEAC ALDTVGWVQR HRKMLRHCPS KRKGSGSGSG SGSGSGSGS GSGSGSGSDY TLDLSVTTVT DYYYPDICSS PCDAELIQTN GKLLLAVFYC LLFVFSLLGN SLVILVLVVC K KLRSITDV YLLNLALSDL LFVFSFPFQT YYLLDQWVFG TVMCKVVSGF YYIGFYSSMF FITLMSVDRY LAVVHAVYAL KV RTIRMGT TLCLAVWLTA IMATIPLLVF YQVASEDGVL QCYSFYNQQT LKWKIFTNFK MNILGLLIPF TIFMFCYIKI LHQ LKRCQN HNKTKAIRLV LIVVIASLLF WVPFNVVLFL TSLHSMHILD GCSISQQLTY ATHVTEIISF THCCVNPVIY AFVG EKFKK HLSEIFQKSC SQIFNYLGRQ MPRESCEKSS SCQQHSSRSS SVDYILGGSD YKDDDDKGGS LEVLFQGPMV SKGEE LFTG VVPILVELDG DVNGHKFSVS GEGEGDATYG KLTLKLICTT GKLPVPWPTL VTTLGYGLQC FARYPDHMKQ HDFFKS AMP EGYVQERTIF FKDDGNYKTR AEVKFEGDTL VNRIELKGID FKEDGNILGH KLEYNYNSHN VYITADKQKN GIKANFK IR HNIEDGGVQL ADHYQQNTPI GDGPVLLPDN HYLSYQSKLS KDPNEKRDHM VLLEFVTAAG ITLGMDELYK GSAWSHPQ F EKGGGSGGGS GGSAWSHPQF EK UniProtKB: C-C motif chemokine 1, C-C chemokine receptor type 8, EGFP |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 43.182078 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MKKHHHHHHH HHHENLYFQG GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECK QYKAVVYSNT IQSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ A CFNRSREY ...String: MKKHHHHHHH HHHENLYFQG GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECK QYKAVVYSNT IQSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ A CFNRSREY QLNDSAAYYL NDLDRIAQPN YIPTQQDVLR TRVKTTGIVE THFTFKDLHF KMFDVGGQRS ERKKWIHCFE GV TAIIFCV ALSDYDLVLA EDEEMNRMHE SMKLFDSICN NKWFTDTSII LFLNKKDLFE EKIKKSPLTI CYPEYAGSNT YEE AAAYIQ CQFEDLNKRK DTKEIYTHFT CATDTKNVQF VFDAVTDVII KNNLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 39.518121 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MHHHHHHHHG ENLYFQGSSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF ...String: MHHHHHHHHG ENLYFQGSSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF LDDNQIVTSS GDTTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FT GHESDIN AICFFPNGNA FATGSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KAD RAGVLA GHDNRVSCLG VTDDGMAVAT GSWDSFLKIW N UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #4: 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: 4 / 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 #5: scFv fragment
| Macromolecule | Name: scFv fragment / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 28.124387 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: AGSDVQLVES GGGLVQPGGS RKLSCSASGF AFSSFGMHWV RQAPEKGLEW VAYISSGSGT IYYADTVKGR FTISRDDPKN TLFLQMTSL RSEDTAMYYC VRSIYYYGSS PFDFWGQGTT LTVSSGGSDI VMTQATSSVP VTPGESVSIS CRSSKSLLHS N GNTYLYWF ...String: AGSDVQLVES GGGLVQPGGS RKLSCSASGF AFSSFGMHWV RQAPEKGLEW VAYISSGSGT IYYADTVKGR FTISRDDPKN TLFLQMTSL RSEDTAMYYC VRSIYYYGSS PFDFWGQGTT LTVSSGGSDI VMTQATSSVP VTPGESVSIS CRSSKSLLHS N GNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TFGAGTKLEL KA AAGNSLV PRGSHHHHHH HH |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
| Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / Formula: NAG |
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| Molecular weight | Theoretical: 221.208 Da |
| Chemical component information | ![]() ChemComp-NAG: |
-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: 7.5 |
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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: FEI FALCON IV (4k x 4k) / Average electron dose: 40.814 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
| Startup model | Type of model: OTHER |
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| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: OTHER / Number images used: 201761 |
| Initial angle assignment | Type: OTHER / Details: Ab initio in cryoSPARC |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
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Keywords
Homo sapiens (human)
Human adenovirus C serotype 2
Authors
Citation




































X (Sec.)
Y (Row.)
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FIELD EMISSION GUN
