1lqv

From Proteopedia

Revision as of 15:57, 12 November 2007

Crystal structure of the Endothelial protein C receptor with phospholipid in the groove in complex with Gla domain of protein C.

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.

Disease

Known diseases associated with this structure: Purpura fulminans, neonatal OMIM:[176860], Thrombophilia due to protein C deficiency OMIM:[176860]

About this Structure

1LQV is a Protein complex structure of sequences from Homo sapiens with NAG, NDG, CA and PTY as ligands. Full crystallographic information is available from OCA.

Reference

The crystal structure of the endothelial protein C receptor and a bound phospholipid., Oganesyan V, Oganesyan N, Terzyan S, Qu D, Dauter Z, Esmon NL, Esmon CT, J Biol Chem. 2002 Jul 12;277(28):24851-4. Epub 2002 May 28. PMID:12034704

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