Structural prediction and analysis of endothelial cell protein C/activatedprotein C receptor

The endothelial cell receptor (EPCR) for protein C (PC)/ activated protein C (APC) is a 221 amino-acid residues long transmembrane glycoprotein with u nclear physiological function, To facilitate future studies and to rational ize recently reported experimental data about this protein, we have constru cted three-dimensional models of human, bovine and mouse EPCR using threadi ng and comparative model building. EPCR is homologous to CD1/MHC class I mo lecules. It consists of two domains, which are similar to the alpha 1 and a lpha 2 domains of MHC class I molecules, whereas the alpha 3 domain of MHC is replaced in EPCR by a transmembrane region followed by a short cytosolic tail, The alpha 1 and alpha 2 domains of CD1/MHC proteins form a groove, w hich binds short peptides, These domains are composed of an eight-stranded antiparallel beta-pleated sheet with two long antiparallel alpha-helices. T he 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 hydr ophobic/aromatic and polar residues with a few charged amino acids. Analysi s of the human EPCR model predicts that (a) the protein does not contain an y calcium binding pockets; (b) C101 and C169 form a buried disulphide bridg e, while C97 is free, and buried in the core of the molecule; and (c) four potential glycosylation sites ate solvent exposed.