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The vitronectin binding area of plasminogen activator inhibitor‐1, mapped by mutagenesis and protection against an inactivating organochemical ligand
Author(s) -
Jensen Jan K,
Wind Troels,
Andreasen Peter A
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02830-2
Subject(s) - vitronectin , serpin , plasminogen activator inhibitor 1 , conformational change , binding site , chemistry , plasminogen activator , biochemistry , microbiology and biotechnology , stereochemistry , biology , receptor , integrin , genetics , gene
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.