The spontaneous polymerization of plasminogen activator inhibitor type-2 and Z-antitrypsin are due to different molecular aberrations
2003 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 537, no 1-3, 11-16 p.Article in journal (Refereed) Published
The wild-type form of plasminogen activator inhibitor type-2 (PAI-2) and the pathogenic Z-mutant of alpha(1)-antitrypsin (alpha(1)AT) are serpins that spontaneously polymerize by the loop-sheet mechanism. Compared to the consensus serpin sequence, both PAI-2 and Z-alpha(1)AT have deviations in the so-called breach region located at the top of the A beta-sheet. In the case of Z-alpha(1)AT, conformational perturbations caused by a single amino acid substitution result in polymerization in vivo and predisposes to disease. To test whether the polymerization of PAI-2 is due to aberrations in the breach region, we constructed substitution mutants of PAI-2 with conserved residues in this region. Analysis of the mutants revealed that deviations in the breach region modulate but are not the major cause of PAI-2 polymerization. Rather, PAI-2 exists in a highly polymerogenic conformation and does not require conformational rearrangements before polymerization can take place.
Place, publisher, year, edition, pages
2003. Vol. 537, no 1-3, 11-16 p.
Serpin, Loop–sheet polymerization, Plasminogen activator inhibitor type-2
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-3836DOI: 10.1016/S0014-5793(03)00057-7PubMedID: 12606023OAI: oai:DiVA.org:umu-3836DiVA: diva2:142717