S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding
2014 | journal article; research paper
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S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding
Alegre-Cebollada, J.; Kosuri, P.; Giganti, D.; Eckels, E.; Rivas-Pardo, J. A.; Hamdani, N. & Warren, C. M. et al. (2014)
Cell, 156(6) pp. 1235-1246. DOI: https://doi.org/10.1016/j.cell.2014.01.056
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Details
- Authors
- Alegre-Cebollada, Jorge; Kosuri, Pallav; Giganti, David; Eckels, Edward; Rivas-Pardo, Jaime Andrés; Hamdani, Nazha; Warren, Chad M.; Solaro, R. John; Linke, Wolfgang A. ; Fernández, Julio M.
- Abstract
- The giant elastic protein titin is a determinant factor in how much blood fills the left ventricle during diastole and thus in the etiology of heart disease. Titin has been identified as a target of S-glutathionylation, an end product of the nitric-oxide-signaling cascade that increases cardiac muscle elasticity. However, it is unknown how S-glutathionylation may regulate the elasticity of titin and cardiac tissue. Here, we show that mechanical unfolding of titin immunoglobulin (Ig) domains exposes buried cysteine residues, which then can be S-glutathionylated. S-glutathionylation of cryptic cysteines greatly decreases the mechanical stability of the parent Ig domain as well as its ability to fold. Both effects favor a more extensible state of titin. Furthermore, we demonstrate that S-glutathionylation of cryptic cysteines in titin mediates mechanochemical modulation of the elasticity of human cardiomyocytes. We propose that posttranslational modification of cryptic residues is a general mechanism to regulate tissue elasticity.
- Issue Date
- 2014
- Journal
- Cell
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie - Working Group
- RG Linke (Kardiovaskuläre Physiologie)
- ISSN
- 1097-4172
- Language
- English