title: The endothelial cell binding determinant of human factor IX resides in the gamma-carboxyglutamic acid domain.
abstract: The blood coagulation factor IX(a) binds specifically to a site on endothelial cells with a Kd of 2.0-3.0 nM. A number of previous studies have attempted to define the region(s) of factor IX(a) that mediate this interaction. These studies suggested that there are two regions of factor IX(a), the gamma-carboxyglutamic acid (Gla) domain and the epidermal growth factor like (EGF-like) domains, that mediate high-affinity binding to endothelial cells. Recently, however, the participation of the EGF1 domain has been excluded from the interaction. This indicated that if there was an EGF component of factor IX contributing to the binding affinity, then it must be in the second EGF-like domain. In order to further evaluate this relationship, we performed competitive binding experiments between 125I plasma factor IX and a set of six chimeric proteins composed of portions of factor VII and factor IX. Our data suggest that the high-affinity interaction between factor IX and the endothelial cell binding site is mediated by the factor IX Gla domain and that the factor IX EGF domains are not involved in binding specificity.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill 27599.
authors.forename: J R
authors.initials: JR
authors.lastname: Toomey
authors.forename: K J
authors.initials: KJ
authors.lastname: Smith
authors.forename: H R
authors.initials: HR
authors.lastname: Roberts
authors.forename: D W
authors.initials: DW
authors.lastname: Stafford
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D004730:Endothelium, Vascular / Q000378:metabolism*; D005164:Factor IX / Q000737:chemistry* / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D015055:1-Carboxyglutamic Acid; D005167:Factor VII; D005164:Factor IX