Structural prediction and analysis of endothelial cell protein C/activated protein 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 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 alpha1 and alpha2 domains of MHC class I molecules, whereas the alpha3 domain of MHC is replaced in EPCR by a transmembrane region followed by a short cytosolic tail. The alpha1 and alpha2 domains of CD1/MHC proteins form a groove, which binds short peptides. These domains are composed of an eight-stranded antiparallel beta-pleated sheet with two long antiparallel alpha-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.
Villoutreix
B O
BO
Lund University, The Wallenberg Laboratory, Department of Clinical Chemistry, University Hospital Malmö, S-205 02 Malmö, Sweden.
Blom
A M
AM
Dahlbäck
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001779:Blood Coagulation Factors; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D001779:Blood Coagulation Factors; D015395:Histocompatibility Antigens Class I; D011956:Receptors, Cell Surface; C091963:activated protein C receptor; D002118:Calcium