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The spontaneous pol...
The spontaneous polymerization of plasminogen activator inhibitor type-2 and Z-antitrypsin are due to different molecular aberrations
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- Wilczynska, Malgorzata (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Lobov, Sergei (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Ny, Tor (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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(creator_code:org_t)
- 2003
- 2003
- English.
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In: FEBS Letters. - 0014-5793 .- 1873-3468. ; 537:1-3, s. 11-16
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Keyword
- Serpin
- Loop–sheet polymerization
- Plasminogen activator inhibitor type-2
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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