The vitronectin binding area of plasminogen activator inhibitor-1, mapped by mutagenesis and protection against an inactivating organochemical ligand

• Published in: FEBS letters 2002-06, Vol.521 (1), p.91-94
• Main Authors: Jensen, Jan K, Wind, Troels, Andreasen, Peter A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Bis-ANS; bis-ANS, 4,4′-dianilino-1,1′-bisnaphthyl-5,5′-disulfonic acid; h, α-helix; Humans; Models, Molecular; Molecular Sequence Data; PAI-1, plasminogen activator inhibitor-1; Plasminogen; Plasminogen Activator Inhibitor 1 - chemistry; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen activator inhibitor-1; Protein Structure, Tertiary; s, β-strand; Serpin; uPA, urokinase-type plasminogen activator; Vitronectin; Vitronectin - chemistry; VN, vitronectin
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02830-2

A distinguishing feature of serpins is their ability to undergo a conformational change consisting in insertion of the reactive centre loop (RCL) into β-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 β-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 α-helix F, β-strand 2A, and α-helix E. Our results contribute to elucidating the unique serpin conformational change.