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Title | Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1. |
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Journal, issue, pages | Structure, Vol. 31, Issue 10, Page 1174-11183.e4, Year 2023 |
Publish date | Oct 5, 2023 |
Authors | Sai Sundar Rajan Raghavan / Louise Turner / Rasmus W Jensen / Nicolai Tidemand Johansen / Daniel Skjold Jensen / Pontus Gourdon / Jinqiu Zhang / Yong Wang / Thor Grundtvig Theander / Kaituo Wang / Thomas Lavstsen / |
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 ...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. |
External links | Structure / PubMed:37582356 |
Methods | EM (single particle) |
Resolution | 3.2 - 3.8 Å |
Structure data | EMDB-16415, PDB-8c3y: EMDB-16416, PDB-8c44: |
Chemicals | ChemComp-PTY: ChemComp-NAG: |
Source |
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Keywords | CELL ADHESION / Plasmodium falciparum / Cerebral Malaria / PfEMP1 / EPCR |