title: The vitronectin binding area of plasminogen activator inhibitor-1, mapped by mutagenesis and protection against an inactivating organochemical ligand.
abstract: A distinguishing feature of serpins is their ability to undergo a conformational change consisting in insertion of the reactive centre loop (RCL) into beta-sheet A. In the serpin plasminogen activator inhibitor-1 (PAI-1), RCL movements are regulated by vitronectin, having a previously poorly defined binding site lateral to PAI-1's beta-sheet A. Using a novel strategy, based on identification of amino acid residues necessary for vitronectin protection of PAI-1 against inactivation by 4,4'-dianilino-1,1'-bisnaphthyl-5,5'-disulfonic acid, we have defined a vitronectin binding surface spanning 10 residues between alpha-helix F, beta-strand 2A, and alpha-helix E. Our results contribute to elucidating the unique serpin conformational change.
authors.affiliation: Laboratory of Cellular Protein Science, Department of Molecular and Structural Biology, Aarhus University, 10C Gustav Wied's Vej, 8000 C Aarhus, Denmark. jkj@mbio.aau.dk
authors.forename: Jan K
authors.initials: JK
authors.lastname: Jensen
authors.forename: Troels
authors.initials: T
authors.lastname: Wind
authors.forename: Peter A
authors.initials: PA
authors.lastname: Andreasen
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D019096:Vitronectin / Q000737:chemistry*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin