7PI6

Trypanosoma brucei ISG65 bound to human complement C3d

Summary for 7PI6

• Entry DOI: 10.2210/pdb7pi6/pdb
• Descriptor: 65 kDa invariant surface glycoprotein, Complement C3dg fragment, GLYCEROL, ... (5 entities in total)
• Functional Keywords: complement, innate immunity, host-pathogen, sleeping sickness, immune system
• Biological source: Trypanosoma brucei brucei (strain 927/4 GUTat10.1); More
• Total number of polymer chains: 4
• Total formula weight: 154743.35

Authors

Cook, A.D.,Higgins, M.K. (deposition date: 2021-08-19, release date: 2022-07-27, Last modification date: 2024-10-16)

Primary citation

Macleod, O.J.S.,Cook, A.D.,Webb, H.,Crow, M.,Burns, R.,Redpath, M.,Seisenberger, S.,Trevor, C.E.,Peacock, L.,Schwede, A.,Kimblin, N.,Francisco, A.F.,Pepperl, J.,Rust, S.,Voorheis, P.,Gibson, W.,Taylor, M.C.,Higgins, M.K.,Carrington, M.
Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor.
Nat Commun, 13:5085-5085, 2022

PubMed Abstract: African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.

PubMed: 36038546
DOI: 10.1038/s41467-022-32728-9

Experimental method

X-RAY DIFFRACTION (2.6 Å)