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Open data
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Basic information
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Title | Structure of CXCR2 bound to CXCL3 (CXCR2-CXCL3-Go Full map) | |||||||||
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![]() | GPCR / Arrestin / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() interleukin-8-mediated signaling pathway / metanephric tubule morphogenesis / negative regulation of neutrophil apoptotic process / mast cell granule / interleukin-8 receptor activity / interleukin-8 binding / acute inflammatory response to antigenic stimulus / C-X-C chemokine receptor activity / CXCR chemokine receptor binding / neutrophil activation ...interleukin-8-mediated signaling pathway / metanephric tubule morphogenesis / negative regulation of neutrophil apoptotic process / mast cell granule / interleukin-8 receptor activity / interleukin-8 binding / acute inflammatory response to antigenic stimulus / C-X-C chemokine receptor activity / CXCR chemokine receptor binding / neutrophil activation / mu-type opioid receptor binding / C-C chemokine receptor activity / corticotropin-releasing hormone receptor 1 binding / C-C chemokine binding / positive regulation of vascular permeability / vesicle docking involved in exocytosis / chemokine-mediated signaling pathway / positive regulation of neutrophil chemotaxis / chemokine activity / Chemokine receptors bind chemokines / dendritic cell chemotaxis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / midbrain development / postsynaptic modulation of chemical synaptic transmission / negative regulation of insulin secretion / cellular defense response / positive regulation of cardiac muscle cell apoptotic process / G protein-coupled serotonin receptor binding / muscle contraction / adenylate cyclase-inhibiting serotonin receptor signaling pathway / adenylate cyclase regulator activity / neutrophil chemotaxis / secretory granule membrane / GABA-ergic synapse / locomotory behavior / calcium-mediated signaling / G protein-coupled receptor activity / receptor internalization / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / mitotic spindle / 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 / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / positive regulation of angiogenesis / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / chemotaxis / Vasopressin regulates renal water homeostasis via Aquaporins / microtubule cytoskeleton / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / antimicrobial humoral immune response mediated by antimicrobial peptide / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / 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) / presynaptic membrane / G protein activity / cell body / GTPase binding / positive regulation of cytosolic calcium ion concentration / Ca2+ pathway / retina development in camera-type eye / cellular response to lipopolysaccharide / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (s) signalling events / G alpha (q) signalling events Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.38 Å | |||||||||
![]() | Sano FK / Saha S / Sharma S / Ganguly M / Shihoya W / Nureki O / Shukla AK / Banerjee R | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis of promiscuous chemokine binding and structural mimicry at the C-X-C chemokine receptor, CXCR2. Authors: Shirsha Saha / Fumiya K Sano / Saloni Sharma / Manisankar Ganguly / Sudha Mishra / Annu Dalal / Hiroaki Akasaka / Takaaki A Kobayashi / Nashrah Zaidi / Divyanshu Tiwari / Nabarun Roy / ...Authors: Shirsha Saha / Fumiya K Sano / Saloni Sharma / Manisankar Ganguly / Sudha Mishra / Annu Dalal / Hiroaki Akasaka / Takaaki A Kobayashi / Nashrah Zaidi / Divyanshu Tiwari / Nabarun Roy / Manish K Yadav / Nilanjana Banerjee / Sayantan Saha / Samanwita Mohapatra / Yuzuru Itoh / Andy Chevigné / Ramanuj Banerjee / Wataru Shihoya / Osamu Nureki / Arun K Shukla / ![]() ![]() Abstract: Selectivity of natural agonists for their cognate receptors is a hallmark of G-protein-coupled receptors (GPCRs); however, this selectivity often breaks down at the chemokine receptors. Chemokines ...Selectivity of natural agonists for their cognate receptors is a hallmark of G-protein-coupled receptors (GPCRs); however, this selectivity often breaks down at the chemokine receptors. Chemokines often display promiscuous binding to chemokine receptors, but the underlying molecular determinants remain mostly elusive. Here, we perform a comprehensive transducer-coupling analysis, testing all known C-X-C chemokines on every C-X-C type chemokine receptor to generate a global fingerprint of the selectivity and promiscuity encoded within this system. Taking lead from this, we determine cryoelectron microscopy (cryo-EM) structures of the most promiscuous receptor, C-X-C chemokine receptor 2 (CXCR2), in complex with several chemokines. These structural snapshots elucidate the details of ligand-receptor interactions, including structural motifs, which are validated using mutagenesis and functional experiments. We also observe that most chemokines position themselves on CXCR2 as a dimer while CXCL6 exhibits a monomeric binding pose. Taken together, our findings provide the molecular basis of chemokine promiscuity at CXCR2 with potential implications for developing therapeutic molecules. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 48.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 24 KB 24 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.9 KB | Display | ![]() |
Images | ![]() | 71.8 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
Others | ![]() ![]() | 48.9 MB 48.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 969.5 KB | Display | ![]() |
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Full document | ![]() | 969 KB | Display | |
Data in XML | ![]() | 15.4 KB | Display | |
Data in CIF | ![]() | 19.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8xx3MC ![]() 8xvuC ![]() 8xwaC ![]() 8xwfC ![]() 8xwmC ![]() 8xwnC ![]() 8xwsC ![]() 8xwvC ![]() 8xx6C ![]() 8xx7C ![]() 8xxhC ![]() 8xxrC ![]() 8xxxC 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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0375 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_38744_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_38744_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : C-X-C chemokine receptor type 2 in complex with C-X-C motif chemo...
Entire | Name: C-X-C chemokine receptor type 2 in complex with C-X-C motif chemokine 3 and Go |
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Components |
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-Supramolecule #1: C-X-C chemokine receptor type 2 in complex with C-X-C motif chemo...
Supramolecule | Name: C-X-C chemokine receptor type 2 in complex with C-X-C motif chemokine 3 and Go type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: C-X-C motif chemokine 3
Macromolecule | Name: C-X-C motif chemokine 3 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.876251 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ASVVTELRCQ CLQTLQGIHL KNIQSVNVRS PGPHCAQTEV IATLKNGKKA CLNPASPMVQ KIIEKILNKG STN UniProtKB: C-X-C motif chemokine 3 |
-Macromolecule #2: C-X-C chemokine receptor type 2
Macromolecule | Name: C-X-C chemokine receptor type 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 46.699609 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSEDF NMESDSFEDF WKGEDLSNYS YSSTLPPFL LDAAPCEPES LEINKYFVVI IYALVFLLSL LGNSLVMLVI LYSRVGRSVT DVYLLNLALA DLLFALTLPI W AASKVNGW ...String: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSEDF NMESDSFEDF WKGEDLSNYS YSSTLPPFL LDAAPCEPES LEINKYFVVI IYALVFLLSL LGNSLVMLVI LYSRVGRSVT DVYLLNLALA DLLFALTLPI W AASKVNGW IFGTFLCKVV SLLKEVNFYS GILLLACISV DRYLAIVHAT RTLTQKRYLV KFICLSIWGL SLLLALPVLL FR RTVYSSN VSPACYEDMG NNTANWRMLL RILPQSFGFI VPLLIMLFCY GFTLRTLFKA HMGQKHRAMR VIFAVVLIFL LCW LPYNLV LLADTLMRTQ VIQETCERRN HIDRALDATE ILGILHSCLN PLIYAFIGQK FRHGLLKILA IHGLISKDSL PKDS RPSFV GSSSGHTSTT L UniProtKB: C-X-C chemokine receptor type 2 |
-Macromolecule #3: Guanine nucleotide-binding protein G(o) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(o) subunit alpha / type: protein_or_peptide / ID: 3 / 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 #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: 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 #5: 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: 5 / 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 #6: Antibody fragment ScFv16
Macromolecule | Name: Antibody fragment ScFv16 / type: protein_or_peptide / ID: 6 / 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 |
-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 | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Average electron dose: 50.2 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: SwissModel / Chain - Initial model type: in silico model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
Output model | ![]() PDB-8xx3: |