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Yorodumi- EMDB-14708: Trypanosoma brucei gambiense ISG65 in complex with human compleme... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14708 | |||||||||
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Title | Trypanosoma brucei gambiense ISG65 in complex with human complement component C3b | |||||||||
Map data | ||||||||||
Sample |
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Keywords | complex / complement / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / 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 ...oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / 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 glucose transmembrane transport / complement-dependent cytotoxicity / complement activation, alternative pathway / complement activation / endopeptidase inhibitor activity / neuron remodeling / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / Purinergic signaling in leishmaniasis infection / Peptide ligand-binding receptors / complement activation, classical pathway / fatty acid metabolic process / Regulation of Complement cascade / Post-translational protein phosphorylation / response to bacterium / positive regulation of receptor-mediated endocytosis / positive regulation of angiogenesis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / azurophil granule lumen / G alpha (i) signalling events / secretory granule lumen / blood microparticle / 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) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.59 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_14708.map.gz | 120.2 MB | EMDB map data format | |
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Header (meta data) | emd-14708-v30.xml emd-14708.xml | 19 KB 19 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14708_fsc.xml | 13.3 KB | Display | FSC data file |
Images | emd_14708.png | 78.2 KB | ||
Filedesc metadata | emd-14708.cif.gz | 6.9 KB | ||
Others | emd_14708_half_map_1.map.gz emd_14708_half_map_2.map.gz | 226.9 MB 226.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14708 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14708 | HTTPS FTP |
-Related structure data
Related structure data | 7zgkMC 7zgjC 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_14708.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: 0.828 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_14708_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_14708_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 C3b |
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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 C3b 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: Complement C3b alpha chain
Supramolecule | Name: Complement C3b alpha chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #4: 65kDa invariant surface glycoprotein
Supramolecule | Name: 65kDa invariant surface glycoprotein / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Trypanosoma brucei gambiense (eukaryote) |
-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 C3b alpha' chain
Macromolecule | Name: Complement C3b alpha' chain / 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: 104.074148 KDa |
Sequence | String: SNLDEDIIAE ENIVSRSEFP ESWLWNVEDL KEPPKNGIST KLMNIFLKDS ITTWEILAVS MSDKKGICVA DPFEVTVMQD FFIDLRLPY SVVRNEQVEI RAVLYNYRQN QELKVRVELL HNPAFCSLAT TKRRHQQTVT IPPKSSLSVP YVIVPLKTGL Q EVEVKAAV ...String: SNLDEDIIAE ENIVSRSEFP ESWLWNVEDL KEPPKNGIST KLMNIFLKDS ITTWEILAVS MSDKKGICVA DPFEVTVMQD FFIDLRLPY SVVRNEQVEI RAVLYNYRQN QELKVRVELL HNPAFCSLAT TKRRHQQTVT IPPKSSLSVP YVIVPLKTGL Q EVEVKAAV YHHFISDGVR KSLKVVPEGI RMNKTVAVRT LDPERLGREG VQKEDIPPAD LSDQVPDTES ETRILLQGTP VA QMTEDAV DAERLKHLIV TPSGCGEENM IGMTPTVIAV HYLDETEQWE KFGLEKRQGA LELIKKGYTQ QLAFRQPSSA FAA FVKRAP STWLTAYVVK VFSLAVNLIA IDSQVLCGAV KWLILEKQKP DGVFQEDAPV IHQEMIGGLR NNNEKDMALT AFVL ISLQE AKDICEEQVN SLPGSITKAG DFLEANYMNL QRSYTVAIAG YALAQMGRLK GPLLNKFLTT AKDKNRWEDP GKQLY NVEA TSYALLALLQ LKDFDFVPPV VRWLNEQRYY GGGYGSTQAT FMVFQALAQY QKDAPDHQEL NLDVSLQLPS RSSKIT HRI HWESASLLRS EETKENEGFT VTAEGKGQGT LSVVTMYHAK AKDQLTCNKF DLKVTIKPAP ETEKRPQDAK NTMILEI CT RYRGDQDATM SILDISMMTG FAPDTDDLKQ LANGVDRYIS KYELDKAFSD RNTLIIYLDK VSHSEDDCLA FKVHQYFN V ELIQPGAVKV YAYYNLEESC TRFYHPEKED GKLNKLCRDE LCRCAEENCF IQKSDDKVTL EERLDKACEP GVDYVYKTR LVKVQLSNDF DEYIMAIEQT IKSGSDEVQV GQQRTFISPI KCREALKLEE KKHYLMWGLS SDFWGEKPNL SYIIGKDTWV EHWPEEDEC QDEENQKQCQ DLGAFTESMV VFGCPN 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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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 K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 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: 3.0 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |