Protein Engineering, Vol. 12, No. 10, 833-840,
October 1999
© 1999 Oxford University Press
Structural prediction and analysis of endothelial cell protein C/activated protein C receptor
Lund University, The Wallenberg Laboratory, Department of Clinical Chemistry, University Hospital Malmö, S-205 02 Malmö, Sweden
The endothelial cell receptor (EPCR) for protein C (PC)/activated protein C (APC) is a 221 amino-acid residues long transmembrane glycoprotein with unclear physiological function. To facilitate future studies and to rationalize recently reported experimental data about this protein, we have constructed three-dimensional models of human, bovine and mouse EPCR using threading and comparative model building. EPCR is homologous to CD1/MHC class I molecules. It consists of two domains, which are similar to the 
1 and 2 domains of MHC class I molecules, whereas the 3 domain of MHC is replaced in EPCR by a transmembrane region followed by a short cytosolic tail. The 1 and 2 domains of CD1/MHC proteins form a groove, which binds short peptides. These domains are composed of an eight-stranded antiparallel ß-pleated sheet with two long antiparallel -helices. The distance between the helical segments dictates the width of the groove. The cleft in EPCR appears to be relatively narrow and it is lined with hydrophobic/aromatic and polar residues with a few charged amino acids. Analysis of the human EPCR model predicts that (a) the protein does not contain any calcium binding pockets; (b) C101 and C169 form a buried disulphide bridge, while C97 is free, and buried in the core of the molecule; and (c) four potential glycosylation sites are solvent exposed.
Keywords: activated protein C receptor/endothelial cell protein C/structural prediction
1 To whom correspondence should be addressed; email: bruno.villoutreix{at}klkemi.mas.lu.se
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