Deformation Model for Thioredoxin Catalysis of Disulfide Bond Dissociation by Force

Pereverzev, Yuriy V.; Prezhdo, Oleg V.

doi:10.1007/s12195-009-0058-6

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…The decrease in disulfide bond length, however, seems to be specific for cystine. How this shortening of disulfide bond length at low forces is related to catch-binding (1,31) could not yet be understood, and remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Force Can Fine-Tune Redox Potentials of Disulfide Bonds

Baldus

Gräter

2012

Biophysical Journal

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Mechanical force applied along a disulfide bond alters its rate of reduction. We here aimed at quantifying the direct effect of force onto the chemical reactivity of a sulfur-sulfur bond in contrast to indirect, e.g., steric or mechanistic, influences. To this end, we evaluated the dependency of a disulfide bond's redox potential on a pulling force applied along the system. Our QM/MM simulations of cystine as a model system take conformational dynamics and explicit solvation into account and show that redox potentials increase over the whole range of forces probed here (30-3320 pN), and thus even in the absence of a significant disulfide bond elongation (<500 pN). Instead, at low forces, dihedrals and angles, as the softer degrees of freedom are stretched, contribute to the destabilization of the oxidized state. We find physiological forces to be likely to tune the disulfide's redox potentials to an extent similar to the tuning within proteins by point mutations.

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Section: Discussionmentioning

confidence: 99%

Mechanical Force Can Fine-Tune Redox Potentials of Disulfide Bonds

Baldus

Gräter

2012

Biophysical Journal

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“…Different mechanisms have been assumed in these models, such as single 50 or dual bound states 51,52 with two dissociation pathways (Fig. 1B), force-regulated dynamic disorder 53,54 , combined entropic-controlled dissociation and energetic-controlled rupture 55 , deformation 56,57 , allostery (Fig. 3B) 58-61 , and sliding-rebinding 62,63 mechanisms.…”

Section: Slip Catch and Ideal Bondsmentioning

confidence: 99%

Mechanochemitry: A Molecular Biomechanics View of Mechanosensing

Zhu

2013

Ann Biomed Eng

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Molecular biomechanics includes two themes: the study of mechanical aspects of biomolecules and the study of molecular biology of the cell using mechanical tools. The two themes are interconnected for obvious reasons. The present review focuses on one of the interconnected areas – the mechanical regulation of molecular interaction and conformational change. Recent conceptual developments are summarized, including catch bonds, regulation of molecular interaction by the history of force application, and cyclic mechanical reinforcement. These studies elucidate the mechanochemistry of some of the candidate mechanosensing molecules, thereby providing a natural connection to mechanobiology.

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“…Proteins and other biological molecules are flexible objects that exhibit an ensemble of conformations at ambient temperatures. The ensemble perspective on protein properties is being actively explored by the biophysical community (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). In thermodynamics equilibrium, each conformation is present with some probability, whose value depends on external parameters, e.g., temperature.…”

Section: Introductionmentioning

confidence: 99%

The Two-Pathway Model of the Biological Catch-Bond as a Limit of the Allosteric Model

Pereverzev

Prezhdo

Sokurenko

2011

Biophysical Journal

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Catch-binding is a counterintuitive phenomenon in which the lifetime of a receptor/ligand bond increases when a force is applied to break the bond. Several mechanisms have been proposed to rationalize catch-binding. In the two-pathway model, the force drives the system away from its native dissociation pathway into an alternative pathway involving a higher energy barrier. Here, we analyze an allosteric model suggesting that a force applied to the complex alters the distribution of receptor conformations, and as a result, induces changes in the ligand-binding site. The model assumes explicitly that the allosteric transitions govern the properties of the ligand site. We demonstrate that the dynamics of the ligand is described by two relaxation times, one of which arises from the allosteric site. Therefore, we argue that one can characterize the allosteric transitions by studying the receptor/ligand binding. We show that the allosteric description reduces to the two-pathway model in the limit when the allosteric transitions are faster than the bond dissociation. The formal results are illustrated with two systems, P-selectin/PSGL-1 and FimH/mannose, subjected to both constant and time-dependent forces. The report advances our understanding of catch-binding by combining alternative physical models into a unified description and makes the problem more tractable for the bond mechanics community.

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Deformation Model for Thioredoxin Catalysis of Disulfide Bond Dissociation by Force

Cited by 4 publications

References 31 publications

Mechanical Force Can Fine-Tune Redox Potentials of Disulfide Bonds

Mechanical Force Can Fine-Tune Redox Potentials of Disulfide Bonds

Mechanochemitry: A Molecular Biomechanics View of Mechanosensing

The Two-Pathway Model of the Biological Catch-Bond as a Limit of the Allosteric Model

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