Plasminogen activator inhibitor type 2 : a unique serpin with two mobile loops

TL;DRAbstract

The superfamily of serine protease inhibitors (serpins) is a large group of proteins with diverse functions but a common tertiary structure. Active serpins are highly metastable molecules. Metastability is the property underlying the success and ubiquitousness of serpins. However, serpin metastability also accounts for improper conformational changes in serpin mutants which may result in pathological serpin polymerization. Plasminogen activator inhibitor type 2 (PAI-2) is a member of the subfamily of ov-serpins. It is the only wild-type (wt) serpin that spontaneously polymerizes under physiological conditions. Another unique feature of PAI-2 is the loop connecting helices C and D (the CD-loop), which is the longest among known serpins and is involved in interactions with the environment. Two partially overlapping goals were achieved during this thesis. The first was to study the molecular determinants involved in PAI-2 polymerization. By using in vitro mutagenesis in combination with b

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