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Structural Bases of...
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Lobov, SergeiUmeå universitet,Institutionen för medicinsk kemi och biofysik
(author)
Structural Bases of the Redox-dependent Conformational Switch in the Serpin PAI-2
- Article/chapterEnglish2004
Publisher, publication year, extent ...
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Elsevier BV,2004
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-14771
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-14771URI
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https://doi.org/10.1016/j.jmb.2004.10.010DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Depending on the redox-status, the serpin plasminogen activator inhibitor type 2 (PAI-2) can exist in either a stable monomeric or polymerogenic form. The latter form, which spontaneously forms loop-sheet polymers, has an open β-sheet A and is stabilized by a disulfide bond between C79 (in the CD-loop) and C161 (at the bottom of PAI-2). Reduction of this bond results in a closing of the β-sheet A and converts PAI-2 to a stable monomeric form. Here we show that the stable monomeric and polymerogenic forms of PAI-2 are fully interconvertible, depending on redox-status of the environment. Our intramolecular distance measurements indicate that the CD-loop folds mainly on one side of the stable monomeric form of the inhibitor. However, the loop can translocate about 54 Å to the bottom of PAI-2 so that the C79–C161 disulfide bond can form under oxidizing conditions. We show also that the redox-active C79 can form a disulfide-link to the matrix protein vitronectin, suggesting that vitronectin can stabilize active PAI-2 in extracellular compartments. PAI-2 is therefore a rare example of a redox-sensitive protein for which the activity and polymerization ability are regulated by reversible disulfide bond formation leading to major translocation of a loop and significant conformational changes in the molecule.
Subject headings and genre
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PAI-2
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redox
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serpin
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vitronectin
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homo-transfer
Added entries (persons, corporate bodies, meetings, titles ...)
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Wilczynska, MalgorzataUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)mawi0006
(author)
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Bergström, FredrikUmeå universitet,Kemiska institutionen
(author)
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Johansson, Lennart B-ÅUmeå universitet,Kemiska institutionen(Swepub:umu)lejo0007
(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:Journal of Molecular Biology: Elsevier BV344:5, s. 1359-680022-2836
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