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The spontaneous pol...
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Wilczynska, MalgorzataUmeå universitet,Institutionen för medicinsk kemi och biofysik
(author)
The spontaneous polymerization of plasminogen activator inhibitor type-2 and Z-antitrypsin are due to different molecular aberrations
- Article/chapterEnglish2003
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Numbers
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LIBRIS-ID:oai:DiVA.org:umu-3836
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-3836URI
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https://doi.org/10.1016/S0014-5793(03)00057-7DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
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Serpin
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Loop–sheet polymerization
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Plasminogen activator inhibitor type-2
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Lobov, SergeiUmeå universitet,Institutionen för medicinsk kemi och biofysik
(author)
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Ny, TorUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)tony0001
(author)
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Umeå universitetInstitutionen för medicinsk kemi och biofysik
(creator_code:org_t)
Related titles
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In:FEBS Letters537:1-3, s. 11-160014-57931873-3468
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