The structural basis of complement inhibition by the human parasite Trypanosoma brucei gambiense

Hagen Sülzen1,2, Jitka Votrubova1, Martin Zoltner3, Sami Kereiche1, Arun Dhillon1, Adriana Merciakova1, Sebastian Zoll1

1Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo namesti 2, 16610 Prague 6, Czech Republic 

2Charles University, Faculty of Science, Albertov 6, 12800 Prague 2, Czech Republic

3Charles University, Faculty of Science, Department of Parasitology, BIOCEV, Vestec, Czech Republic


African trypanosomes have developed elaborate mechanisms to avoid clearance by the human immune system. While many of the defence systems have been described in detail, the basis of alternative pathway inhibition remains obscure. Trypanosomes are unaffected by complement-mediated lysis but the molecular processes that prevent formation of the membrane attack complex are currently not understood. Recently we have identified the trypanosome surface receptor that interacts with complement factor 3, the central hub of the complement cascade, and determined its complex structure by single particle cryo-EM. Using an interdisciplinary approach combining biochemical, biophysical, structural and cell biological methods we provide detailed insight into the unusual molecular mechanism of complement inhibition by an important human pathogen.