1L8J

Crystal Structure of the Endothelial Protein C Receptor and Bound Phospholipid Molecule

1L8J の概要

• エントリーDOI: 10.2210/pdb1l8j/pdb
• 分子名称: Endothelial protein C receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: protein-lipid complex, glycosilation, mhc class1, hydrophobic groove, blood clotting
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24053.80

構造登録者

Oganesyan, V.,Oganesyan, N.,Terzyan, S.,Dongfeng, Q.,Dauter, Z.,Esmon, N.L.,Esmon, C.T. (登録日: 2002-03-20, 公開日: 2002-06-26, 最終更新日: 2024-11-06)

主引用文献

Oganesyan, V.,Oganesyan, N.,Terzyan, S.,Qu, D.,Dauter, Z.,Esmon, N.L.,Esmon, C.T.
The crystal structure of the endothelial protein C receptor and a bound phospholipid.
J.Biol.Chem., 277:24851-24854, 2002

PubMed Abstract: The endothelial cell protein C receptor (EPCR) shares approximately 20% sequence identity with the major histocompatibility complex class 1/CD1 family of molecules, accelerates the thrombin-thrombomodulin-dependent generation of activated protein C, a natural anticoagulant, binds to activated neutrophils, and can undergo translocation from the plasma membrane to the nucleus. Blocking protein C/activated protein C binding to the receptor inhibits not only protein C activation but the ability of the host to respond appropriately to bacterial challenge, exacerbating both the coagulant and inflammatory responses. To understand how EPCR accomplishes these multiple tasks, we solved the crystal structure of EPCR alone and in complex with the phospholipid binding domain of protein C. The structures were strikingly similar to CD1d. A tightly bound phospholipid resides in the groove typically involved in antigen presentation. The protein C binding site is outside this conserved groove and is distal from the membrane-spanning domain. Extraction of the lipid resulted in loss of protein C binding, which could be restored by lipid reconstitution. CD1d augments the immune response by presenting glycolipid antigens. The EPCR structure is a model for how CD1d binds lipids and further suggests additional potential functions for EPCR in immune regulation, possibly including the anti-phospholipid syndrome.

PubMed: 12034704
DOI: 10.1074/jbc.C200163200

実験手法

X-RAY DIFFRACTION (2 Å)