4V3D

The CIDRa domain from HB3var03 PfEMP1 bound to endothelial protein C receptor

4V3D の概要

• エントリーDOI: 10.2210/pdb4v3d/pdb
• 関連するPDBエントリー: 4V3E
• 分子名称: HB3VAR03 CIDRA DOMAIN, ENDOTHELIAL PROTEIN C RECEPTOR, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: signaling protein, pfemp1, epcr, malaria, cidr domain, endothelial protein c receptor
• 由来する生物種: PLASMODIUM FALCIPARUM; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 102888.75

構造登録者

Lau, C.K.Y.,Turner, L.,Jespersen, J.S.,Lowe, E.D.,Petersen, B.,Wang, C.W.,Petersen, J.E.V.,Lusingu, J.,Theander, T.G.,Lavstsen, T.,Higgins, M.K. (登録日: 2014-10-17, 公開日: 2014-12-17, 最終更新日: 2024-11-13)

主引用文献

Lau, C.K.Y.,Turner, L.,Jespersen, J.S.,Lowe, E.D.,Petersen, B.,Wang, C.W.,Petersen, J.E.V.,Lusingu, J.,Theander, T.G.,Lavstsen, T.,Higgins, M.K.
Structural Conservation Despite Huge Sequence Diversity Allows Epcr Binding by the Pfemp1 Family Implicated in Severe Childhood Malaria.
Cell Host Microbe., 17:118-, 2015

PubMed Abstract: 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 CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 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 CIDRα1 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.

PubMed: 25482433
DOI: 10.1016/J.CHOM.2014.11.007

実験手法

X-RAY DIFFRACTION (2.65 Å)