The vitronectin binding area of plasminogen activator inhibitor-1, mapped by mutagenesis and protection against an inactivating organochemical ligand.
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.
Jensen
Jan K
JK
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
Wind
Troels
T
Andreasen
Peter A
PA
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*
D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin