King's College London

Research portal

Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)438-450.e5
JournalMOLECULAR CELL
Volume69
Issue number3
Early online date18 Jan 2018
DOIs
Accepted/In press20 Dec 2017
E-pub ahead of print18 Jan 2018
Published1 Feb 2018

Documents

King's Authors

Abstract

S-nitrosation, commonly referred to as S-nitrosylation, is widely regarded as a ubiquitous, stable post-translational modification that directly regulates many proteins. Such a widespread role would appear to be incompatible with the inherent lability of the S-nitroso bond, especially its propensity to rapidly react with thiols to generate disulfide bonds. As anticipated, we observed robust and widespread protein S-nitrosation after exposing cells to nitrosocysteine or lipopolysaccharide. Proteins detected using the ascorbate-dependent biotin switch method are typically interpreted to be directly regulated by S-nitrosation. However, these S-nitrosated proteins are shown to predominantly comprise transient intermediates leading to disulfide bond formation. These disulfides are likely to be the dominant end effectors resulting from elevations in nitrosating cellular nitric oxide species. We propose that S-nitrosation primarily serves as a transient intermediate leading to disulfide formation. Overall, we conclude that the current widely held perception that stable S-nitrosation directly regulates the function of many proteins is significantly incorrect.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454