Model for Stretching and Unfolding the Giant Multidomain Muscle Protein Using Single-Molecule Force Spectroscopy

Staple, Douglas B.; Payne, S.H.; Reddin, Andrew L. C.; Kreuzer, H. J.

doi:10.1103/physrevlett.101.248301

Cited by 41 publications

(27 citation statements)

References 26 publications

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“…A hierarchy of unfolding energies of the unfolding crystals may be simply due to inhomogeneity effects of the crystal domains [14,35,56], showing variable bond-breaking barriers [33] possibly owing to interfacial energy effects [57]. Another important effect is anisotropicity of the crystals with respect to the force direction-different paths in the wiggly energy landscape lead to different unfolding energy barriers [58]-so that different unfolding forces can be induced by variable crystal orientations in the macromolecule.…”

Section: Unfolding Energy Hierarchymentioning

confidence: 99%

“…We remark that to avoid the introduced di-block approximation, not always experimentally verified, one needs to evaluate the partition function [32,33] and only numerical results in the discrete model can be obtained. Moreover, stochastic processes considering fluctuations in both the unfolding forces [48] and the unfolding lengths are possible extensions of the proposed model.…”

Section: Energetic Assumptionsmentioning

confidence: 99%

“…More recently, in [33], a statistical mechanics-based model for the stretching of titin proteins has been proposed, considering also the influence of the AFM loading device. A simple Ising model, neglecting the elasticity of both folded and unfolded domains in protein macromolecules, was instead proposed in [34] to describe the statistics of unfolding events.…”

Section: Introductionmentioning

confidence: 99%

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An energetic model for macromolecules unfolding in stretching experiments

Tommasi

Millardi

Puglisi

et al. 2013

J. R. Soc. Interface.

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We propose a simple approach, based on the minimization of the total (entropic plus unfolding) energy of a two-state system, to describe the unfolding of multidomain macromolecules (proteins, silks, polysaccharides, nanopolymers). The model is fully analytical and enlightens the role of the different energetic components regulating the unfolding evolution. As an explicit example, we compare the analytical results with a titin atomic force microscopy stretch-induced unfolding experiment showing the ability of the model to quantitatively reproduce the experimental behaviour. In the thermodynamic limit, the sawtooth force-elongation unfolding curve degenerates to a constant force unfolding plateau.

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Section: Unfolding Energy Hierarchymentioning

confidence: 99%

Section: Energetic Assumptionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An energetic model for macromolecules unfolding in stretching experiments

Tommasi

Millardi

Puglisi

et al. 2013

J. R. Soc. Interface.

View full text Add to dashboard Cite

show abstract

“…60,61 Proteins β-sheet secondary structures, such as FN or silk, display a sawtooth force-extension curve with mean force-peaks of 145-300 pN (Figure 4), where individual force peaks correspond to the mechanical unfolding of specific domains. 56,58,60,62 Not only do protein unfolding forces depend the free-energy barrier (ΔG T-N ), the intrinsic transition distance (Δz) between folded and unfolded domains also regulates peak forces. The interplay between ΔG T-N and Δz in regulating unfolding forces can be understood using Bell's two state model.…”

Section: Testing the Mechanical Durability Of Protein Textilesmentioning

confidence: 99%

Protein-Based Textiles: Bio-Inspired and Bio-Derived Materials for Medical and Non-Medical Applications

Deravi¹,

Golecki²,

Parker³

2013

Journal of Chemical and Biological Interfaces

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The hierarchical structure-dependent function of self-assembling proteins regulates the biochemical and mechanical functions of cells, tissues, and organs. These multi-scale properties make proteins desirable candidates for novel supramolecular materials that require tailored properties and customizable functions. The ability to translate molecular domains of proteins into the bulk production of conformable materials, such as textiles, is restricted by the current limitations in fabrication technologies and the finite abundance of protein starting material. We will review the common features of self-assembling proteins, including their structure-dependent mechanical properties and how these characteristics have inspired techniques for manufacturing protein-based textiles. These technologies coupled with recent advances in recombinant protein synthesis enable the bulk production of fibers and fabrics that emulate the hierarchical function of natural protein networks.

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“…The IMP is represented as a freely jointed chain of CG beads, where each CG bead represents three amino acids and has a diameter of 8 Å, equal to the Kuhn length of a polypeptide chain (51,52). To avoid a frameshift in the mapping of amino acids to CG beads upon a loop-swap sequence modification, dummy atoms were introduced, as described previously (2).…”

Section: Description Of the Cg Simulationsmentioning

confidence: 99%

Improving membrane protein expression by optimizing integration efficiency

Niesen¹,

Marshall²,

Miller

et al. 2017

Journal of Biological Chemistry

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The heterologous overexpression of integral membrane proteins in Escherichia coli often yields insufficient quantities of purifiable protein for applications of interest. The current study leverages a recently demonstrated link between co-translational membrane integration efficiency and protein expression levels to predict protein sequence modifications that improve expression. Membrane integration efficiencies, obtained using a coarse-grained simulation approach, robustly predicted effects on expression of the integral membrane protein TatC for a set of 140 sequence modifications, including loop-swap chimeras and single-residue mutations distributed throughout the protein sequence. Mutations that improve simulated integration efficiency were 4-fold enriched with respect to improved experimentally observed expression levels. Furthermore, the effects of double mutations on both simulated integration efficiency and experimentally observed expression levels were cumulative and largely independent, suggesting that multiple mutations can be introduced to yield higher levels of purifiable protein. This work provides a foundation for a general method for the rational overexpression of integral membrane proteins based on computationally simulated membrane integration efficiencies. Integral membrane proteins (IMPs)4 play crucial roles in the transport of molecules, energy, and information across the membrane and are an important focus of structural and biophysical studies. However, the production of sufficient levels of IMPs is a limiting factor in their characterization (1). Even among homologous IMP sequences, expression levels can vary widely (1-6), and the mechanistic basis for this variability is often unclear. Extensive efforts have been committed to identify IMP sequences, expression conditions, and host modifications that yield IMP expression at sufficient levels for further study (7-10). Despite these efforts, general guidelines for successful overexpression for IMPs are lacking.Biogenesis of IMPs in Escherichia coli involves multiple steps that are potential bottlenecks for overexpression, including correct targeting to the inner membrane (11, 12), membrane integration (2, 13-17), and folding (18 -21). For a given sequence, understanding how each of these steps affects observed expression levels may lead to improved strategies for IMP overexpression.Previous work indicates that the Sec-facilitated membrane integration step of biogenesis is a limiting factor in the overexpression of the TatC IMP (2). Sequence changes in the C-tail that alter the efficiency of membrane integration efficiency, determined either from coarse-grained (CG) simulations or experimentally, were shown to correlate with experimentally observed IMP expression levels. Further work is necessary to explore the generality of this link and its potential for enabling the rational enhancement of IMP expression.The current study demonstrates the predictive capacity of simulated integration efficiency for experimental expression by examining a wide...

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Model for Stretching and Unfolding the Giant Multidomain Muscle Protein Using Single-Molecule Force Spectroscopy

Cited by 41 publications

References 26 publications

An energetic model for macromolecules unfolding in stretching experiments

An energetic model for macromolecules unfolding in stretching experiments

Protein-Based Textiles: Bio-Inspired and Bio-Derived Materials for Medical and Non-Medical Applications

Improving membrane protein expression by optimizing integration efficiency

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