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Seminar: Linking Mechanochemistry to protein folding at the single bond level

on Monday the 7th of November there will be a  seminar of probable interest to many IQTCUB members given by:
Prof. Sergi Garcia-Manyes (Kings College London) – visiting Ismael Diaz,
“Linking Mechanochemistry to protein folding at the single bond level”

Time: 12:00
Place: Sala d’Actes, department of Physical Chemistry.


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. [Beedle et al., Nature Communications 7, 12490, 2016]