Difference between revisions of "Part:BBa K3582101"

Revision as of 14:54, 20 October 2020

CD201(ENDOTHELIAL PROTEIN C RECEPTOR)

Endothelial cell protein C receptor (EPCR) was initially identified and cloned as an endothelial transmembrane glycoprotein, which is cell-specific and capable of binding to protein C and activated protein C (APC). EPCR plays a crucial role in protein C activation by the thrombin-thrombomodulin (TM) complex. Recent studies showed that EPCR plays a critical role in supporting APC-mediated cytoprotective signalling and have demonstrated that EPCR also binds with other ligands. Sequestration of erythrocytes infected with Plasmodium falciparum in host blood vessels is a key cause in the pathogenesis of severe childhood malaria. Specific interactions between the P. falciparum erythrocyte membrane protein 1 (PfEMP1) and receptors on the endothelial lining mediates this sequestration. The endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, is identified as the endothelial receptor for DC8 and DC13 PfEMP1. N-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and group A PfEMP1 subfamilies mediate the EPCR binding, and that CIDRα1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways. It has implications for understanding malaria pathology and the development of new malaria interventions. EPCR protein is an N-glycosylated type I membrane protein that exhibits a sequence and three-dimensional homology with the major histocompatibility class 1(MHC class 1)/CD1 family of proteins. Having a deep groove characterises this family of proteins and is usually used for antigen binding in other proteins in the family, but not in EPCR. In the case of CD1c and CD1d, this groove is filled with a lipid antigen, usually a glycolipid. EPCR also has a lipid in the corresponding groove like the CD1 series. In this case, the lipid is usually phosphatidylcholine, but it may be phosphatidylethanolamine. The bound lipid contributes to protein C binding, but its structure suggests a role in maintaining the EPCR structure rather than contributing directly to protein C binding.

Figure 1. Gene sequence aligned with their annotations.

Sequence and Features

References

• https://www.rcsb.org/structure/4v3e
• https://www.uniprot.org/uniprot/Q9UNN8
• Endothelial cell protein C receptor: a multiliganded and multifunctional receptor.(2014 Sep 4).PubMed Central (PMC).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155268/
• Kenji Fukudome,Recent Advances in Thrombosis and Hemostasis 2008 pp 211-217,Structure

and Function of the Endothelial Cell Protein C Receptor