| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 28, 24851-24854, July 12, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The endothelial cell protein C
receptor (EPCR) shares ~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.
The atomic coordinates and the structure factors (code 1L8J and 1LQV) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
ACCELERATED PUBLICATION
The Crystal Structure of the Endothelial Protein C
Receptor and a Bound Phospholipid*
,,
,§**§§
Cardiovascular Biology Research Program,
§ Howard Hughes Medical Institute, and ¶ Department of
Crystallography, Oklahoma Medical Research Foundation, Oklahoma City,
Oklahoma 73104, SAIC/NCI-Frederick, National Institutes
of Health, Frederick, Maryland 21702, and the Departments
of ** Pathology and Biochemistry
and Molecular Biology, University of Oklahoma Health Sciences
Center, Oklahoma City, Oklahoma 73104
*
This research was supported by Specialized Centers of
Research Grant P50 HL54502 awarded by the National Institutes of
Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Diao and E. Tajkhorshid Indirect Role of Ca2+ in the Assembly of Extracellular Matrix Proteins Biophys. J., July 1, 2008; 95(1): 120 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xue, L. March, P. N Sambrook, K. Fukudome, and C. J Jackson Endothelial protein C receptor is overexpressed in rheumatoid arthritic (RA) synovium and mediates the anti-inflammatory effects of activated protein C in RA monocytes Ann Rheum Dis, December 1, 2007; 66(12): 1574 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yang, J.-S. Bae, C. Manithody, and A. R. Rezaie Identification of a Specific Exosite on Activated Protein C for Interaction with Protease-activated Receptor 1 J. Biol. Chem., August 31, 2007; 282(35): 25493 - 25500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ndonwi, G. J. Broze Jr., S. Agah, A. E. Schmidt, and S. P. Bajaj Substitution of the Gla Domain in Factor X with That of Protein C Impairs Its Interaction with Factor VIIa/Tissue Factor: LACK OF COMPARABLE EFFECT BY SIMILAR SUBSTITUTION IN FACTOR IX J. Biol. Chem., May 25, 2007; 282(21): 15632 - 15644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. O. Mosnier, B. V. Zlokovic, and J. H. Griffin The cytoprotective protein C pathway Blood, April 15, 2007; 109(8): 3161 - 3172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Bae, L. Yang, C. Manithody, and A. R. Rezaie Engineering a Disulfide Bond to Stabilize the Calcium-binding Loop of Activated Protein C Eliminates Its Anticoagulant but Not Its Protective Signaling Properties J. Biol. Chem., March 23, 2007; 282(12): 9251 - 9259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Bae, L. Yang, and A. R. Rezaie Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cells PNAS, February 20, 2007; 104(8): 2867 - 2872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. S. Preston, E. Ajzner, C. Razzari, S. Karageorgi, S. Dua, B. Dahlback, and D. A. Lane Multifunctional Specificity of the Protein C/Activated Protein C Gla Domain J. Biol. Chem., September 29, 2006; 281(39): 28850 - 28857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Balazs, A. J. Fabian, C. T. Esmon, and R. C. Mulligan Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow Blood, March 15, 2006; 107(6): 2317 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Li, X. Zheng, J.-M. Gu, G. L. Ferrell, M. Brady, N. L. Esmon, and C. T. Esmon Extraembryonic expression of EPCR is essential for embryonic viability Blood, October 15, 2005; 106(8): 2716 - 2722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Saaren-Seppala, M. Jauhiainen, T. M. T. Tervo, B. Redl, P. K. J. Kinnunen, and J. M. Holopainen Interaction of Purified Tear Lipocalin with Lipid Membranes Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3649 - 3656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Dahlback and B. O. Villoutreix Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway: Novel Insights Into Structure-Function Relationships and Molecular Recognition Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1311 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Finigan, S. M. Dudek, P. A. Singleton, E. T. Chiang, J. R. Jacobson, S. M. Camp, S. Q. Ye, and J. G. N. Garcia Activated Protein C Mediates Novel Lung Endothelial Barrier Enhancement: ROLE OF SPHINGOSINE 1-PHOSPHATE RECEPTOR TRANSACTIVATION J. Biol. Chem., April 29, 2005; 280(17): 17286 - 17293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Klein and N. Nikolaidis The descent of the antibody-based immune system by gradual evolution PNAS, January 4, 2005; 102(1): 169 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Hurtado, R. Montes, J.-C. Gris, M. L. Bertolaccini, A. Alonso, M. A. Martinez-Gonzalez, M. A. Khamashta, K. Fukudome, D. A. Lane, and J. Hermida Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death Blood, September 1, 2004; 104(5): 1369 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. de Wouwer, D. Collen, and E. M. Conway Thrombomodulin-Protein C-EPCR System: Integrated to Regulate Coagulation and Inflammation Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1374 - 1383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Saposnik, J.-L. Reny, P. Gaussem, J. Emmerich, M. Aiach, and S. Gandrille A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis Blood, February 15, 2004; 103(4): 1311 - 1318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Rezaie and L. Yang Thrombomodulin allosterically modulates the activity of the anticoagulant thrombin PNAS, October 14, 2003; 100(21): 12051 - 12056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Marsh Lipid-binding proteins: Structure of the phospholipid ligands Protein Sci., September 1, 2003; 12(9): 2109 - 2117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Esmon The Protein C Pathway Chest, September 1, 2003; 124(3_suppl): 26S - 32S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Esmon Coagulation and inflammation Innate Immunity, June 1, 2003; 9(3): 192 - 198. [Abstract] [PDF]
|
|
|
|
|
|
J.-M. Gu, J. T. B. Crawley, G. Ferrell, F. Zhang, W. Li, N. L. Esmon, and C. T. Esmon Disruption of the Endothelial Cell Protein C Receptor Gene in Mice Causes Placental Thrombosis and Early Embryonic Lethality J. Biol. Chem., November 1, 2002; 277(45): 43335 - 43343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Esmon New Mechanisms for Vascular Control of Inflammation Mediated by Natural Anticoagulant Proteins J. Exp. Med., September 2, 2002; 196(5): 561 - 564. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
