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

FEBS Letters

Jensen, Jan K¹  Wind, Troels¹  Andreasen, Peter A¹ 

[1] Laboratory of Cellular Protein Science, Department of Molecular and Structural Biology, Aarhus University, 10C Gustav Wied's Vej, 8000 C Aarhus, Denmark

关键词: Bis-ANS;    Plasminogen activator inhibitor-1;    Plasminogen;    Serpin;    Vitronectin;    bis-ANS;    4;    4′-dianilino-1;    1′-bisnaphthyl-5;    5′-disulfonic acid;    h;    α-helix;    PAI-1;    plasminogen activator inhibitor-1;    s;    β-strand;    uPA;    urokinase-type plasminogen activator;    VN;    vitronectin;   

DOI  :  10.1016/S0014-5793(02)02830-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown