7ZGK

Trypanosoma brucei gambiense ISG65 in complex with human complement component C3b

Summary for 7ZGK

• Entry DOI: 10.2210/pdb7zgk/pdb
• EMDB information: 14708
• Descriptor: Complement C3 beta chain, Complement C3b alpha' chain, 65 kDa invariant surface glycoprotein, putative (3 entities in total)
• Functional Keywords: complex, complement, immune system
• Biological source: Trypanosoma brucei gambiense; More
• Total number of polymer chains: 3
• Total formula weight: 216290.98

Authors

Suelzen, H.,Zoll, S. (deposition date: 2022-04-03, release date: 2023-04-05, Last modification date: 2024-10-16)

Primary citation

Sulzen, H.,Began, J.,Dhillon, A.,Kereiche, S.,Pompach, P.,Votrubova, J.,Zahedifard, F.,Subrtova, A.,Safner, M.,Hubalek, M.,Thompson, M.,Zoltner, M.,Zoll, S.
Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.
Nat Commun, 14:2403-2403, 2023

PubMed 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 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.

PubMed: 37105991
DOI: 10.1038/s41467-023-37988-7

Experimental method

ELECTRON MICROSCOPY (3.59 Å)