Abstract
The study of mechanical unfolding, through the combined efforts of atomic force microscopy and simulation, is yielding fresh insights into the free-energy landscapes of proteins. Thus far, experiments have been mostly analyzed with one-dimensional models of the free-energy landscape. We show that as the two ends of a protein, filamin, are pulled apart at a speed tending to zero, the measured mechanical strength plateaus at approximately 30 pN instead of going toward zero, deviating from the Bell model. The deviation can only be explained by a switch between parallel pathways. Insightful analysis of mechanical unfolding kinetics needs to account for the multidimensionality of the free-energy landscapes of proteins, which are crucial for understanding the behavior of proteins under the small forces experienced in vivo.
Highlights
Zu Thur Yew Institute of Molecular and Cell Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
Insightful analysis of mechanical unfolding kinetics needs to account for the multidimensionality of the free-energy landscapes of proteins, which are crucial for understanding the behavior of proteins under the small forces experienced in vivo
Single-molecule techniques such as atomic force microscopy and optical tweezers have been extensively used to probe the mechanical resistance of proteins by measuring the unfolding force or equivalently, the unfolding time
Summary
Experiments on protein-ligand complexes performed in a broad range of pulling velocities have shown that the unfolding kinetics at low velocities can show strong deviations from the Bell model. We report the mechanical unfolding kinetics of dictyostelium discoideum filamin domain 4 ͑ddFLN4͒ in a broad range of pulling velocities and observed, in a singledomain protein, a strong deviation from the Bell model at very low pulling velocities.
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