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The length of the reactive center loop modulates the latency transition of plasminogen activator inhibitor‐1
Author(s) -
Na YuRan,
Im Hana
Publication year - 2005
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.041063705
Subject(s) - chemistry , plasminogen activator , plasminogen activator inhibitor 1 , transition (genetics) , activator (genetics) , loop (graph theory) , microbiology and biotechnology , biochemistry , biology , genetics , gene , mathematics , combinatorics
Plasminogen activator inhibitor‐1 (PAI‐1) belongs to the serine protease inhibitor (serpin) protein family, which has a common tertiary structure consisting of three β‐sheets and several α‐helices. Despite the similarity of its structure with those of other serpins, PAI‐1 is unique in its conformational lability, which allows the conversion of the metastable active form to a more stable latent conformation under physiological conditions. For the conformational conversion to occur, the reactive center loop (RCL) of PAI‐1 must be mobilized and inserted into the major β‐sheet, A sheet. In an effort to understand how the structural conversion is regulated in this conformationally labile serpin, we modulated the length of the RCL of PAI‐1. We show that releasing the constraint on the RCL by extension of the loop facilitates a conformational transition of PAI‐1 to a stable state. Biochemical data strongly suggest that the stabilization of the transformed conformation is owing to the insertion of the RCL into A β‐sheet, as in the known latent form. In contrast, reducing the loop length drastically retards the conformational change. The results clearly show that the constraint on the RCL is a factor that regulates the conformational transition of PAI‐1.