1lqv: Difference between revisions
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|PDB= 1lqv |SIZE=350|CAPTION= <scene name='initialview01'>1lqv</scene>, resolution 1.6Å | |PDB= 1lqv |SIZE=350|CAPTION= <scene name='initialview01'>1lqv</scene>, resolution 1.6Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1l8j|1L8J]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lqv OCA], [http://www.ebi.ac.uk/pdbsum/1lqv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lqv RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Oganesyan, V.]] | [[Category: Oganesyan, V.]] | ||
[[Category: Terzyan, S.]] | [[Category: Terzyan, S.]] | ||
[[Category: ca ion binding]] | [[Category: ca ion binding]] | ||
[[Category: gla (gamma-carboxyglutamic acid) residue]] | [[Category: gla (gamma-carboxyglutamic acid) residue]] | ||
[[Category: phospholipid binding groove]] | [[Category: phospholipid binding groove]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:06:15 2008'' | ||
