1L8J
Crystal Structure of the Endothelial Protein C Receptor and Bound Phospholipid Molecule
Summary for 1L8J
| Entry DOI | 10.2210/pdb1l8j/pdb |
| Descriptor | 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) |
| Functional Keywords | protein-lipid complex, glycosilation, mhc class1, hydrophobic groove, blood clotting |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 24053.80 |
| Authors | Oganesyan, V.,Oganesyan, N.,Terzyan, S.,Dongfeng, Q.,Dauter, Z.,Esmon, N.L.,Esmon, C.T. (deposition date: 2002-03-20, release date: 2002-06-26, Last modification date: 2020-07-29) |
| Primary citation | 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 Cited by 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: 12034704DOI: 10.1074/jbc.C200163200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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