8C44

HB3VAR03 apo headstructure (PfEMP1 A) complexed with EPCR

Summary for 8C44

• Entry DOI: 10.2210/pdb8c44/pdb
• EMDB information: 16416
• Descriptor: PfEMP1, Endothelial protein C receptor, PHOSPHATIDYLETHANOLAMINE, ... (4 entities in total)
• Functional Keywords: plasmodium falciparum, cerebral malaria, pfemp1, epcr, cell adhesion
• Biological source: Plasmodium falciparum HB3; More
• Total number of polymer chains: 2
• Total formula weight: 165585.94

Authors

Raghavan, S.S.R.,Lavstsen, T.,Wang, K.T. (deposition date: 2022-12-31, release date: 2023-08-16, Last modification date: 2024-10-23)

Primary citation

Rajan Raghavan, S.S.,Turner, L.,Jensen, R.W.,Johansen, N.T.,Jensen, D.S.,Gourdon, P.,Zhang, J.,Wang, Y.,Theander, T.G.,Wang, K.,Lavstsen, T.
Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1.
Structure, 31:1174-1183.e4, 2023

PubMed Abstract: 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 CIDRα1 domains interact with the adjacent DBLα1 domain through central, conserved residues of the EPCR-binding site to adopt a compact conformation. Upon EPCR binding, the DBLα1 domain is displaced, and the EPCR-binding helix of CIDRα1 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.

PubMed: 37582356
DOI: 10.1016/j.str.2023.07.011

Experimental method

ELECTRON MICROSCOPY (3.2 Å)