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-Structure paper
タイトル | 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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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 2403, Year 2023 |
掲載日 | 2023年4月27日 |
著者 | 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 / |
PubMed 要旨 | 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. |
リンク | Nat Commun / PubMed:37105991 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.58 - 3.59 Å |
構造データ | EMDB-14707, PDB-7zgj: EMDB-14708, PDB-7zgk: |
由来 |
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キーワード | IMMUNE SYSTEM / complement / complex |