Molecular fluctuations as a ruler of force-induced protein conformations
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Andrew Stannard Marc Mora Amy EM Beedle Marta Castro-López Stephanie Board Sergi Garcia-ManyesAbstract
Molecular fluctuations directly reflect the underlying energy landscape. Variance analysis examines protein dynamics in several biochemistry-driven approaches, yet measurement of probe-independent fluctuations in proteins exposed to mechanical forces remains only accessible through steered molecular dynamics simulations. Using single molecule magnetic tweezers, here we conduct variance analysis to show that individual unfolding and refolding transitions occurring in dynamic equilibrium in a single protein under force are hallmarked by a change in the protein's end-to-end fluctuations, revealing a change in protein stiffness. By unfolding and refolding three structurally distinct proteins under a wide range of constant forces, we demonstrate that the associated change in protein compliance to reach force-induced thermodynamically stable states scales with the protein's contour length increment, in agreement with the sequence-independent freely jointed chain model of polymer physics. Our findings will help elucidate the conformational dynamics of proteins exposed to mechanical force at high resolution which are of central importance in mechanosensing and mechanotransduction.
Journal details
Journal Nano Letters
Volume 21
Issue number 7
Pages 2953-2961
Available online
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Publisher website (DOI) 10.1021/acs.nanolett.1c00051
Europe PubMed Central 33765390
Pubmed 33765390
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