Protein S-sulfenylation is a fleeting molecular switch that regulates non-enzymatic oxidative folding

19Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

Abstract

The post-translational modification S-sulfenylation functions as a key sensor of oxidative stress. Yet the dynamics of sulfenic acid in proteins remains largely elusive due to its fleeting nature. Here we use single-molecule force-clamp spectroscopy and mass spectrometry to directly capture the reactivity of an individual sulfenic acid embedded within the core of a single Ig domain of the titin protein. Our results demonstrate that sulfenic acid is a crucial short-lived intermediate that dictates the protein's fate in a conformation-dependent manner. When exposed to the solution, sulfenic acid rapidly undergoes further chemical modification, leading to irreversible protein misfolding; when cryptic in the protein's microenvironment, it readily condenses with a neighbouring thiol to create a protective disulfide bond, which assists the functional folding of the protein. This mechanism for non-enzymatic oxidative folding provides a plausible explanation for redox-modulated stiffness of proteins that are physiologically exposed to mechanical forces, such as cardiac titin.

Cite

CITATION STYLE

APA

Beedle, A. E. M., Lynham, S., & Garcia-Manyes, S. (2016). Protein S-sulfenylation is a fleeting molecular switch that regulates non-enzymatic oxidative folding. Nature Communications, 7. https://doi.org/10.1038/ncomms12490

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free