Structural highlights
Function
A0A0L7KL67_PLAFX
Publication Abstract from PubMed
Severe Plasmodium falciparum malaria infections are caused by microvascular sequestration of parasites binding to the human endothelial protein C receptor (EPCR) via the multi-domain P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands. Using cryogenic electron microscopy (Cryo-EM) and PfEMP1 sequence diversity analysis, we found that group A PfEMP1 CIDRalpha1 domains interact with the adjacent DBLalpha1 domain through central, conserved residues of the EPCR-binding site to adopt a compact conformation. Upon EPCR binding, the DBLalpha1 domain is displaced, and the EPCR-binding helix of CIDRalpha1 is turned, kinked, and twisted to reach a rearranged, stable EPCR-bound conformation. The unbound conformation and the required transition to the EPCR-bound conformation may represent a conformational masking mechanism of immune evasion for the PfEMP1 family.
Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1.,Rajan Raghavan SS, Turner L, Jensen RW, Johansen NT, Jensen DS, Gourdon P, Zhang J, Wang Y, Theander TG, Wang K, Lavstsen T Structure. 2023 Oct 5;31(10):1174-1183.e4. doi: 10.1016/j.str.2023.07.011. Epub , 2023 Aug 14. PMID:37582356[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rajan Raghavan SS, Turner L, Jensen RW, Johansen NT, Jensen DS, Gourdon P, Zhang J, Wang Y, Theander TG, Wang K, Lavstsen T. Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1. Structure. 2023 Oct 5;31(10):1174-1183.e4. PMID:37582356 doi:10.1016/j.str.2023.07.011
