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Mechanical Deformation Accelerates Protein Ageing
Author(s) -
ValleOrero Jessica,
RivasPardo Jaime Andrés,
TapiaRojo Rafael,
Popa Ionel,
Echelman Daniel J.,
Haldar Shubhasis,
Fernández Julio M.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201703630
Subject(s) - ageing , chemistry , biophysics , protein folding , oxidative phosphorylation , unfolded protein response , ascorbic acid , oxidative damage , oxidative stress , biochemistry , biology , endoplasmic reticulum , food science , genetics
A hallmark of tissue ageing is the irreversible oxidative modification of its proteins. We show that single proteins, kept unfolded and extended by a mechanical force, undergo accelerated ageing in times scales of minutes to days. A protein forced to be continuously unfolded completely loses its ability to contract by folding, becoming a labile polymer. Ageing rates vary among different proteins, but in all cases they lose their mechanical integrity. Random oxidative modification of cryptic side chains exposed by mechanical unfolding can be slowed by the addition of antioxidants such as ascorbic acid, or accelerated by oxidants. By contrast, proteins kept in the folded state and probed over week‐long experiments show greatly reduced rates of ageing. We demonstrate a novel approach whereby protein ageing can be greatly accelerated: the constant unfolding of a protein for hours to days is equivalent to decades of exposure to free radicals under physiological conditions.