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TitleCryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 2403, Year 2023
Publish dateApr 27, 2023
AuthorsHagen 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 /
PubMed AbstractAfrican 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.
External linksNat Commun / PubMed:37105991 / PubMed Central
MethodsEM (single particle)
Resolution3.58 - 3.59 Å
Structure data

EMDB-14707, PDB-7zgj:
Trypanosoma brucei gambiense ISG65 in complex with human complement component C3
Method: EM (single particle) / Resolution: 3.58 Å

EMDB-14708, PDB-7zgk:
Trypanosoma brucei gambiense ISG65 in complex with human complement component C3b
Method: EM (single particle) / Resolution: 3.59 Å

Source
  • homo sapiens (human)
  • trypanosoma brucei gambiense (eukaryote)
KeywordsIMMUNE SYSTEM / complement / complex

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