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Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction
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SYSNO ASEP 0572083 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction Author(s) Sülzen, Hagen (UOCHB-X) ORCID
Began, Jakub (UOCHB-X) ORCID, RID
Dhillon, Arun (UOCHB-X)
Kereiche, Sami (UOCHB-X) ORCID
Pompach, Petr (BTO-N)
Votrubová, Jitka (UOCHB-X)
Zahedifard, F. (CZ)
Šubrtová, Adriana (UOCHB-X)
Šafner, Marie (UOCHB-X)
Hubálek, Martin (UOCHB-X) RID, ORCID
Thompson, M. (BE)
Zoltner, M. (CZ)
Zoll, Sebastian (UOCHB-X) ORCIDArticle number 2403 Source Title Nature Communications. - : Nature Publishing Group
Roč. 14, April (2023)Number of pages 18 s. Language eng - English Country US - United States Keywords variant surface glycoprotein ; antigenic determinants ; spontaneous hydrolysis OECD category Biochemistry and molecular biology R&D Projects EF18_046/0015974 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018127 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA22-21612S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 ; BTO-N - RVO:86652036 UT WOS 000989625000023 EID SCOPUS 85157997391 DOI 10.1038/s41467-023-37988-7 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.1038/s41467-023-37988-7
Number of the records: 1