Sökning: onr:"swepub:oai:DiVA.org:umu-14771" >
Structural Bases of...
Structural Bases of the Redox-dependent Conformational Switch in the Serpin PAI-2
-
- Lobov, Sergei (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
-
- Wilczynska, Malgorzata (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
-
- Bergström, Fredrik (författare)
- Umeå universitet,Kemiska institutionen
-
visa fler...
-
- Johansson, Lennart B-Å (författare)
- Umeå universitet,Kemiska institutionen
-
- Ny, Tor (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
-
visa färre...
-
(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- Engelska.
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 344:5, s. 1359-68
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- PAI-2
- redox
- serpin
- vitronectin
- homo-transfer
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas