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Yorodumi- EMDB-35351: Cryo-EM structure of CXCL8 bound C-X-C chemokine receptor 1 in co... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35351 | |||||||||
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Title | Cryo-EM structure of CXCL8 bound C-X-C chemokine receptor 1 in complex with Gi heterotrimer | |||||||||
Map data | sharpened map | |||||||||
Sample |
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Keywords | GPCR / Chemokine / Interleukin / CXCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information interleukin-8 receptor activity / regulation of single stranded viral RNA replication via double stranded DNA intermediate / regulation of entry of bacterium into host cell / interleukin-8 receptor binding / interleukin-8 binding / positive regulation of cellular biosynthetic process / chemokine receptor activity / negative regulation of cell adhesion molecule production / ATF4 activates genes in response to endoplasmic reticulum stress / CXCR chemokine receptor binding ...interleukin-8 receptor activity / regulation of single stranded viral RNA replication via double stranded DNA intermediate / regulation of entry of bacterium into host cell / interleukin-8 receptor binding / interleukin-8 binding / positive regulation of cellular biosynthetic process / chemokine receptor activity / negative regulation of cell adhesion molecule production / ATF4 activates genes in response to endoplasmic reticulum stress / CXCR chemokine receptor binding / embryonic digestive tract development / C-C chemokine receptor activity / neutrophil activation / C-C chemokine binding / induction of positive chemotaxis / cellular response to fibroblast growth factor stimulus / chemokine-mediated signaling pathway / positive regulation of neutrophil chemotaxis / Chemokine receptors bind chemokines / chemokine activity / dendritic cell chemotaxis / negative regulation of G protein-coupled receptor signaling pathway / Interleukin-10 signaling / cellular response to interleukin-1 / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / regulation of cell adhesion / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / neutrophil chemotaxis / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to endoplasmic reticulum stress / Peptide ligand-binding receptors / secretory granule membrane / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / response to molecule of bacterial origin / 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-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 / receptor internalization / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / 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 / positive regulation of angiogenesis / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / chemotaxis / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / antimicrobial humoral immune response mediated by antimicrobial peptide / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / Senescence-Associated Secretory Phenotype (SASP) / cellular response to tumor necrosis factor / retina development in camera-type eye / Ca2+ pathway / heparin binding / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.41 Å | |||||||||
Authors | Ishimoto N / Park JH / Park SY | |||||||||
Funding support | 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural basis of CXC chemokine receptor 1 ligand binding and activation. Authors: Naito Ishimoto / Jae-Hyun Park / Kouki Kawakami / Michiko Tajiri / Kenji Mizutani / Satoko Akashi / Jeremy R H Tame / Asuka Inoue / Sam-Yong Park / Abstract: Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and ...Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers. These GPCRs have therefore been the target of many drug development campaigns and structural studies. Here, we solve the structure of CXCR1 complexed with CXCL8 and cognate G-proteins using cryo-EM, showing the detailed interactions between the receptor, the chemokine and Gαi protein. Unlike the closely related CXCR2, CXCR1 strongly prefers to bind CXCL8 in its monomeric form. The model shows that steric clashes would form between dimeric CXCL8 and extracellular loop 2 (ECL2) of CXCR1. Consistently, transplanting ECL2 of CXCR2 onto CXCR1 abolishes the selectivity for the monomeric chemokine. Our model and functional analysis of various CXCR1 mutants will assist efforts in structure-based drug design targeting specific CXC chemokine receptor subtypes. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35351.map.gz | 28 MB | EMDB map data format | |
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Header (meta data) | emd-35351-v30.xml emd-35351.xml | 28.5 KB 28.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35351_fsc.xml | 6.5 KB | Display | FSC data file |
Images | emd_35351.png | 51.5 KB | ||
Masks | emd_35351_msk_1.map | 29.6 MB | Mask map | |
Others | emd_35351_additional_1.map.gz emd_35351_additional_2.map.gz emd_35351_half_map_1.map.gz emd_35351_half_map_2.map.gz | 26.3 MB 14.8 MB 27.5 MB 27.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35351 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35351 | HTTPS FTP |
-Validation report
Summary document | emd_35351_validation.pdf.gz | 840.3 KB | Display | EMDB validaton report |
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Full document | emd_35351_full_validation.pdf.gz | 839.9 KB | Display | |
Data in XML | emd_35351_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | emd_35351_validation.cif.gz | 17.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35351 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35351 | HTTPS FTP |
-Related structure data
Related structure data | 8ic0MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_35351.map.gz / Format: CCP4 / Size: 29.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.07313 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_35351_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: The map was calculated by deepEMhancer
File | emd_35351_additional_1.map | ||||||||||||
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Annotation | The map was calculated by deepEMhancer | ||||||||||||
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Density Histograms |
-Additional map: map
File | emd_35351_additional_2.map | ||||||||||||
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Annotation | map | ||||||||||||
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Density Histograms |
-Half map: half map 1
File | emd_35351_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_35351_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of human chemokine receptor 1
Entire | Name: Cryo-EM structure of human chemokine receptor 1 |
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Components |
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-Supramolecule #1: Cryo-EM structure of human chemokine receptor 1
Supramolecule | Name: Cryo-EM structure of human chemokine receptor 1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 150 KDa |
-Macromolecule #1: C-X-C chemokine receptor type 1
Macromolecule | Name: C-X-C chemokine receptor type 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.935199 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSNITDPQMW DFDDLNFTGM PPADEDYSPC MLETETLNKY VVIIAYALVF LLSLLGNSLV MLVILYSRVG RSVTDVYLLN LALADLLFA LTLPIWAASK VNGWIFGTFL CKVVSLLKEV NFYSGILLLA CISVDRYLAI VHATRTLTQK RHLVKFVCLG C WGLSMNLS ...String: MSNITDPQMW DFDDLNFTGM PPADEDYSPC MLETETLNKY VVIIAYALVF LLSLLGNSLV MLVILYSRVG RSVTDVYLLN LALADLLFA LTLPIWAASK VNGWIFGTFL CKVVSLLKEV NFYSGILLLA CISVDRYLAI VHATRTLTQK RHLVKFVCLG C WGLSMNLS LPFFLFRQAY HPNNSSPVCY EVLGNDTAKW RMVLRILPHT FGFIVPLFVM LFCYGFTLRT LFKAHMGQKH RA MRVIFAV VLIFLLCWLP YNLVLLADTL MRTQVIQESC ERRNNIGRAL DATEILGFLH SCLNPIIYAF IGQNFRHGFL KIL AMHGLV SKEFLARHRV TSYTSSSVNV SSNLHHHHHH HH UniProtKB: C-X-C chemokine receptor type 1 |
-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: 40.415031 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF 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: 37.728152 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: GPGSSGSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: GPGSSGSELD 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 #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: 8.506765 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #5: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 27.409588 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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 KAAALEVLFQ |
-Macromolecule #6: Interleukin-8
Macromolecule | Name: Interleukin-8 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.401807 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: SAKELRCQCI KTYSKPFHPK FIKELRVIES GPHCANTEII VKLSDGRELC LDPKENWVQR VVEKFLKRAE NS UniProtKB: Interleukin-8 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.0 mg/mL | ||||||||||||||||||||||||
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Buffer | pH: 7.5 Component:
Details: 50 mM HEPES pH8.0, 100 mM NaCl, 1 mM MgCl2, 0.5 mM TCEP, 0.001% LMNG, 0.0001% CHS, 1 uM IL8 | ||||||||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 4175 / Average exposure time: 4.7 sec. / Average electron dose: 51.16 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
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 / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-8ic0: |