The reduced activity of PP-1α under redox stress condition is a consequence of GSH-mediated transient disulfide formation
2018 | journal article; research paper
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
The reduced activity of PP-1α under redox stress condition is a consequence of GSH-mediated transient disulfide formation
Singh, S.; Lämmle, S.; Giese, H.; Kämmerer, S.; Meyer-Roxlau, S. ; Alfar, E. A. & Dihazi, H. et al. (2018)
Scientific Reports, 8(1) art. 17711. DOI: https://doi.org/10.1038/s41598-018-36267-6
Documents & Media
Details
- Authors
- Singh, Simranjit; Lämmle, Simon; Giese, Heiko; Kämmerer, Susanne; Meyer-Roxlau, Stefanie ; Alfar, Ezzaldin Ahmed; Dihazi, Hassan ; Guan, Kaomei ; El-Armouche, Ali ; Richter, Florian
- Abstract
- Heart failure is the most common cause of morbidity and hospitalization in the western civilization. Protein phosphatases play a key role in the basal cardiac contractility and in the responses to β-adrenergic stimulation with type-1 phosphatase (PP-1) being major contributor. We propose here that formation of transient disulfide bridges in PP-1α might play a leading role in oxidative stress response. First, we established an optimized workflow, the so-called “cross-over-read” search method, for the identification of disulfide-linked species using permutated databases. By applying this method, we demonstrate the formation of unexpected transient disulfides in PP-1α to shelter against over-oxidation. This protection mechanism strongly depends on the fast response in the presence of reduced glutathione. Our work points out that the dimerization of PP-1α involving Cys39 and Cys127 is presumably important for the protection of PP-1α active surface in the absence of a substrate. We finally give insight into the electron transport from the PP-1α catalytic core to the surface. Our data suggest that the formation of transient disulfides might be a general mechanism of proteins to escape from irreversible cysteine oxidation and to prevent their complete inactivation.
- Issue Date
- 2018
- Journal
- Scientific Reports
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade
SFB 1002 | A05: Molekulares Imaging von kardialen Calcium-Freisetzungsdomänen - Working Group
- RG El-Armouche
RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling) - ISSN
- 2045-2322
- Language
- English