4v3e

The CIDRa domain from IT4var07 PfEMP1 bound to endothelial protein C receptor

spinqualitylabelsall models 4v3e, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4v3e is a 2 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MAN, NAG, PTY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function EPCR_HUMAN Binds activated protein C. Enhances protein C activation by the thrombin-thrombomodulin complex; plays a role in the protein C pathway controlling blood coagulation. Publication Abstract from PubMed The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRalpha1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRalpha1:EPCR complexes with analysis of 885 CIDRalpha1 sequences, showing that the EPCR-binding surfaces of CIDRalpha1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRalpha1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding. Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria.,Lau CK, Turner L, Jespersen JS, Lowe ED, Petersen B, Wang CW, Petersen JE, Lusingu J, Theander TG, Lavstsen T, Higgins MK Cell Host Microbe. 2014 Dec 3. pii: S1931-3128(14)00423-5. doi:, 10.1016/j.chom.2014.11.007. PMID:25482433 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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