Year: 2020
Type: article
Abstract: As established nearly a century ago, mechanoradicals originate from homolytic bond scission in polymers. The existence, nature and biological relevance of mechanoradicals in proteins, instead, are unknown. We here show that mechanical stress on collagen produces radicals and subsequently reactive oxygen species, essential biological signaling molecules. Electron-paramagnetic resonance (EPR) spectroscopy of stretched rat tail tendon, atomistic molecular dynamics simulations and quantum-chemical calculations show that the radicals form by bond scission in the direct vicinity of crosslinks in collagen. Radicals migrate to adjacent clusters of aromatic residues and stabilize on oxidized tyrosyl radicals, giving rise to a distinct EPR spectrum consistent with a stable dihydroxyphenylalanine (DOPA) radical. The protein mechanoradicals, as a yet undiscovered source of oxidative stress, finally convert into hydrogen peroxide. Our study suggests collagen I to have evolved as a radical sponge against mechano-oxidative damage and proposes a mechanism for exercise-induced oxidative stress and redox-mediated pathophysiological processes.
Source: Nature Communications
Authors: Christopher Zapp, Agnieszka Obarska-Kosinska, Benedikt Rennekamp, Markus Kurth, David M. Hudson, Davide Mercadante, Uladzimir Barayeu, Tobias P. Dick, Vasyl Denysenkov, Thomas Prisner, Marina Bennati, Csaba Daday, Reinhard Kappl, Frauke Gräter
Institutions: Heidelberg University, Heidelberg Institute for Theoretical Studies, Deutsches Elektronen-Synchrotron DESY, European Molecular Biology Laboratory, University of Washington, University of Zurich, German Cancer Research Center, DKFZ-ZMBH Alliance, Goethe University Frankfurt, Max Planck Institute for Biophysical Chemistry, Saarland University
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
OpenAlex ID: W2981925571