Journal article
Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes
WH Tham, CQ Schmidt, RE Hauhart, M Guariento, PB Tetteh-Quarcoo, S Lopaticki, JP Atkinson, PN Barlow, AF Cowman
Blood | Published : 2011
Abstract
The Plasmodium falciparum adhesin PfRh4 binds to complement receptor type-1 (CR1) on human erythrocytes and mediates a glycophorin-independent invasion pathway. CR1 is a complement regulator and immune-adherence receptor on erythrocytes required for shuttling of C3b/C4b-opsonized particles to liver and spleen for phagocytosis. Using recombinant CR1 constructs, we mapped the recognition site for PfRh4 to complement control protein modules 1 to 3 (CCP1-3) at the membrane-distal amino terminus of CR1. This region of CR1 binds to C4b and C3b and accelerates decay of both classic pathway and alternative pathway C3 and C5 convertases. CCP1-3 competed for PfRh4 binding to erythroid CR1 and inhibite..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
The work was supported by the Victorian State Government OIS and National Health and Medical Research Council IRIISS grants (361646). A.F.C. is a Howard Hughes International Scholar and an Australia Fellow from the National Health and Medical Research Council, Australia. P.B.T.-Q. was supported by the Darwin Trust of Edinburgh. C.Q.S. and M.G. were supported by a Wellcome Trust Grant (081179). R.E.H. and J.P.A. were supported by National Institutes of Health grant AI041592.