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Yorodumi- EMDB-14707: Trypanosoma brucei gambiense ISG65 in complex with human compleme... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14707 | |||||||||
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Title | Trypanosoma brucei gambiense ISG65 in complex with human complement component C3 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | complement / complex / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / positive regulation of lipid storage / positive regulation of phagocytosis, engulfment ...C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / positive regulation of lipid storage / positive regulation of phagocytosis, engulfment / positive regulation of G protein-coupled receptor signaling pathway / complement receptor mediated signaling pathway / Activation of C3 and C5 / positive regulation of type IIa hypersensitivity / positive regulation of D-glucose transmembrane transport / complement-dependent cytotoxicity / complement activation / complement activation, alternative pathway / endopeptidase inhibitor activity / neuron remodeling / B cell activation / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / Purinergic signaling in leishmaniasis infection / complement activation, classical pathway / Peptide ligand-binding receptors / fatty acid metabolic process / Regulation of Complement cascade / Post-translational protein phosphorylation / response to bacterium / positive regulation of receptor-mediated endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of angiogenesis / azurophil granule lumen / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / G alpha (i) signalling events / secretory granule lumen / blood microparticle / receptor ligand activity / inflammatory response / immune response / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / signaling receptor binding / Neutrophil degranulation / cell surface / signal transduction / protein-containing complex / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Trypanosoma brucei gambiense (eukaryote) / Homo Sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.58 Å | |||||||||
Authors | Suelzen H / Zoll S | |||||||||
Funding support | Czech Republic, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction. Authors: Hagen Sülzen / Jakub Began / Arun Dhillon / Sami Kereïche / Petr Pompach / Jitka Votrubova / Farnaz Zahedifard / Adriana Šubrtova / Marie Šafner / Martin Hubalek / Maaike Thompson / ...Authors: Hagen Sülzen / Jakub Began / Arun Dhillon / Sami Kereïche / Petr Pompach / Jitka Votrubova / Farnaz Zahedifard / Adriana Šubrtova / Marie Šafner / Martin Hubalek / Maaike Thompson / Martin Zoltner / Sebastian Zoll / Abstract: African Trypanosomes have developed elaborate mechanisms to escape the adaptive immune response, but little is known about complement evasion particularly at the early stage of infection. Here we ...African Trypanosomes have developed elaborate mechanisms to escape the adaptive immune response, but little is known about complement evasion particularly at the early stage of infection. Here we show that ISG65 of the human-infective parasite Trypanosoma brucei gambiense is a receptor for human complement factor C3 and its activation fragments and that it takes over a role in selective inhibition of the alternative pathway C5 convertase and thus abrogation of the terminal pathway. No deposition of C4b, as part of the classical and lectin pathway convertases, was detected on trypanosomes. We present the cryo-electron microscopy (EM) structures of native C3 and C3b in complex with ISG65 which reveal a set of modes of complement interaction. Based on these findings, we propose a model for receptor-ligand interactions as they occur at the plasma membrane of blood-stage trypanosomes and may facilitate innate immune escape of the parasite. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14707.map.gz | 122 MB | EMDB map data format | |
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Header (meta data) | emd-14707-v30.xml emd-14707.xml | 19.7 KB 19.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14707_fsc.xml | 13.2 KB | Display | FSC data file |
Images | emd_14707.png | 73.5 KB | ||
Filedesc metadata | emd-14707.cif.gz | 7.2 KB | ||
Others | emd_14707_half_map_1.map.gz emd_14707_half_map_2.map.gz | 226.5 MB 226.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14707 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14707 | HTTPS FTP |
-Related structure data
Related structure data | 7zgjMC 7zgkC 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_14707.map.gz / Format: CCP4 / Size: 244.1 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: 0.86 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_14707_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_14707_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Trypanosoma brucei gambiense ISG65 in complex with human compleme...
Entire | Name: Trypanosoma brucei gambiense ISG65 in complex with human complement component C3 |
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Components |
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-Supramolecule #1: Trypanosoma brucei gambiense ISG65 in complex with human compleme...
Supramolecule | Name: Trypanosoma brucei gambiense ISG65 in complex with human complement component C3 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Complement C3 beta chain
Supramolecule | Name: Complement C3 beta chain / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: 65 kDa invariant surface glycoprotein
Supramolecule | Name: 65 kDa invariant surface glycoprotein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Trypanosoma brucei gambiense (eukaryote) |
-Supramolecule #4: Complement C3 alpha chain
Supramolecule | Name: Complement C3 alpha chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo Sapiens (human) |
-Macromolecule #1: Complement C3 beta chain
Macromolecule | Name: Complement C3 beta chain / 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: 71.39332 KDa |
Sequence | String: SPMYSIITPN ILRLESEETM VLEAHDAQGD VPVTVTVHDF PGKKLVLSSE KTVLTPATNH MGNVTFTIPA NREFKSEKGR NKFVTVQAT FGTQVVEKVV LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT VNHKLLPVGR TVMVNIENPE GIPVKQDSLS S QNQLGVLP ...String: SPMYSIITPN ILRLESEETM VLEAHDAQGD VPVTVTVHDF PGKKLVLSSE KTVLTPATNH MGNVTFTIPA NREFKSEKGR NKFVTVQAT FGTQVVEKVV LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT VNHKLLPVGR TVMVNIENPE GIPVKQDSLS S QNQLGVLP LSWDIPELVN MGQWKIRAYY ENSPQQVFST EFEVKEYVLP SFEVIVEPTE KFYYIYNEKG LEVTITARFL YG KKVEGTA FVIFGIQDGE QRISLPESLK RIPIEDGSGE VVLSRKVLLD GVQNPRAEDL VGKSLYVSAT VILHSGSDMV QAE RSGIPI VTSPYQIHFT KTPKYFKPGM PFDLMVFVTN PDGSPAYRVP VAVQGEDTVQ SLTQGDGVAK LSINTHPSQK PLSI TVRTK KQELSEAEQA TRTMQALPYS TVGNSNNYLH LSVLRTELRP GETLNVNFLL RMDRAHEAKI RYYTYLIMNK GRLLK AGRQ VREPGQDLVV LPLSITTDFI PSFRLVAYYT LIGASGQREV VADSVWVDVK DSCVGSLVVK SGQSEDRQPV PGQQMT LKI EGDHGARVVL VAVDKGVFVL NKKNKLTQSK IWDVVEKADI GCTPGSGKDY AGVFSDAGLT FTSSSGQQTA QRAELQC PQ PAA UniProtKB: Complement C3 |
-Macromolecule #2: Complement C3
Macromolecule | Name: Complement C3 / 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: 113.169875 KDa |
Sequence | String: SVQLTEKRMD KVGKYPKELR KCCEDGMREN PMRFSCQRRT RFISLGEACK KVFLDCCNYI TELRRQHARA SHLGLARSNL DEDIIAEEN IVSRSEFPES WLWNVEDLKE PPKNGISTKL MNIFLKDSIT TWEILAVSMS DKKGICVADP FEVTVMQDFF I DLRLPYSV ...String: SVQLTEKRMD KVGKYPKELR KCCEDGMREN PMRFSCQRRT RFISLGEACK KVFLDCCNYI TELRRQHARA SHLGLARSNL DEDIIAEEN IVSRSEFPES WLWNVEDLKE PPKNGISTKL MNIFLKDSIT TWEILAVSMS DKKGICVADP FEVTVMQDFF I DLRLPYSV VRNEQVEIRA VLYNYRQNQE LKVRVELLHN PAFCSLATTK RRHQQTVTIP PKSSLSVPYV IVPLKTGLQE VE VKAAVYH HFISDGVRKS LKVVPEGIRM NKTVAVRTLD PERLGREGVQ KEDIPPADLS DQVPDTESET RILLQGTPVA QMT EDAVDA ERLKHLIVTP SGCGEQNMIG MTPTVIAVHY LDETEQWEKF GLEKRQGALE LIKKGYTQQL AFRQPSSAFA AFVK RAPST WLTAYVVKVF SLAVNLIAID SQVLCGAVKW LILEKQKPDG VFQEDAPVIH QEMIGGLRNN NEKDMALTAF VLISL QEAK DICEEQVNSL PGSITKAGDF LEANYMNLQR SYTVAIAGYA LAQMGRLKGP LLNKFLTTAK DKNRWEDPGK QLYNVE ATS YALLALLQLK DFDFVPPVVR WLNEQRYYGG GYGSTQATFM VFQALAQYQK DAPDHQELNL DVSLQLPSRS SKITHRI HW ESASLLRSEE TKENEGFTVT AEGKGQGTLS VVTMYHAKAK DQLTCNKFDL KVTIKPAPET EKRPQDAKNT MILEICTR Y RGDQDATMSI LDISMMTGFA PDTDDLKQLA NGVDRYISKY ELDKAFSDRN TLIIYLDKVS HSEDDCLAFK VHQYFNVEL IQPGAVKVYA YYNLEESCTR FYHPEKEDGK LNKLCRDELC RCAEENCFIQ KSDDKVTLEE RLDKACEPGV DYVYKTRLVK VQLSNDFDE YIMAIEQTIK SGSDEVQVGQ QRTFISPIKC REALKLEEKK HYLMWGLSSD FWGEKPNLSY IIGKDTWVEH W PEEDECQD EENQKQCQDL GAFTESMVVF GCPN UniProtKB: Complement C3 |
-Macromolecule #3: 65 kDa invariant surface glycoprotein, putative
Macromolecule | Name: 65 kDa invariant surface glycoprotein, putative / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Trypanosoma brucei gambiense (eukaryote) / Strain: MHOM/CI/86/DAL972 |
Molecular weight | Theoretical: 40.823516 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGSSHHHHHH SSGLVPRGSH MLLVIGSEDN RVPGDKKLTK EGAAALCKMK HLADKVAKER SQELKDRTQN FAGYIEFELY RIDYWLEKL NGPKGRKDGY AKLSDSDIEK VKEIFNKAKD GITKQLPEAK KAGEEAGKLH TEVKKAAENA RGQDLDDDTA K STGLYRVL ...String: MGSSHHHHHH SSGLVPRGSH MLLVIGSEDN RVPGDKKLTK EGAAALCKMK HLADKVAKER SQELKDRTQN FAGYIEFELY RIDYWLEKL NGPKGRKDGY AKLSDSDIEK VKEIFNKAKD GITKQLPEAK KAGEEAGKLH TEVKKAAENA RGQDLDDDTA K STGLYRVL NWYCITKEER HNATPNCDGI QFRKHYLSVN RSAIDCSSTS YEENYDWSAN ALQVALNSWE DVKPKKLESA GS DKNCNIG QSSESHPCTM TEEWQTPYKE TVEKLRELED AYQRGKKAHD AMLGYANTAY AVNTKVEQEK PLTEVIAAAK EAG KKGAKI IIPAAAPATP TNSTKNDDSA PTEHVDRGIA TNETQVEVGI D UniProtKB: 65 kDa invariant surface glycoprotein, putative |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Component:
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Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 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) / Average electron dose: 41.1 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: 2.5 µm / Nominal defocus min: 1.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |