Molecular mechanism of β‐sheet self‐organization at water‐hydrophobic interfaces

Nikolić, Aleksandra; Baud, Stéphanie; Rauscher, Sarah; Pomès, Régis

doi:10.1002/prot.22854

Cited by 46 publications

(49 citation statements)

References 108 publications

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“…The nontrivial behavior of the driving forces and barriers to assembly at interfaces should be relevant in biological systems where hydrophobicity plays an important role. Experiments have shown that hydrophobic surfaces bind and facilitate the unfolding of proteins, including those that form amyloids (29)(30)(31). Our results shed light on these phenomena and suggest that large hydrophobic surfaces may generically serve as catalysts for unfolding proteins (32), via solvent-mediated interactions.…”

Section: Modelsmentioning

confidence: 58%

Extended surfaces modulate hydrophobic interactions of neighboring solutes

Patel

Varilly

Jamadagni

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

154

224

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Interfaces are a most common motif in complex systems. To understand how the presence of interfaces affects hydrophobic phenomena, we use molecular simulations and theory to study hydration of solutes at interfaces. The solutes range in size from subnanometer to a few nanometers. The interfaces are self-assembled monolayers with a range of chemistries, from hydrophilic to hydrophobic. We show that the driving force for assembly in the vicinity of a hydrophobic surface is weaker than that in bulk water and decreases with increasing temperature, in contrast to that in the bulk. We explain these distinct features in terms of an interplay between interfacial fluctuations and excluded volume effects-the physics encoded in Lum-Chandler-Weeks theory [Lum K, Chandler D, Weeks JD (1999) J Phys Chem B 103:4570-4577]. Our results suggest a catalytic role for hydrophobic interfaces in the unfolding of proteins, for example, in the interior of chaperonins and in amyloid formation. binding | hydrophobicity | thermodynamics H ydrophobic effects are ubiquitous and often the most significant forces of self-assembly and stability of nanoscale structures in liquid matter, from phenomena as simple as micelle formation to those as complex as protein folding and aggregation (1, 2). These effects depend importantly on length scale (3-5). Water molecules near small hydrophobic solutes do not sacrifice hydrogen bonds, but have fewer ways in which to form them, leading to a large negative entropy of hydration. In contrast, hydrogen bonds are broken in the hydration of large solutes, resulting in an enthalpic penalty. For hydrophobic solutes in bulk water at standard conditions, the cross-over from one regime to the other occurs at around 1 nm (3-6) and marks a change in the scaling of the solvation free energy from being linear with solute volume to being linear with exposed surface area. In bulk water, this crossover provides a framework for understanding the assembly of small species into a large aggregate.Typical biological systems contain a high density of interfaces, including those of membranes and proteins, spanning the entire spectrum from hydrophilic to hydrophobic. Whereas water near hydrophilic surfaces is bulk-like in many respects, water near hydrophobic surfaces is different, akin to that near a liquid-vapor interface (3-5, 7-9). Here, we consider how these interfaces alter hydrophobic effects. Specifically, to shed light on the thermodynamics of hydration at, binding to, and assembly at interfaces, we study solutes with a range of sizes at various self-assembled monolayer interfaces over a range of temperatures using molecular simulations and theory.Our principal results are that, although the hydration thermodynamics of hydrophobic solutes at hydrophilic surfaces is similar to that in bulk, changing from entropic to enthalpic with increasing solute size, it is enthalpic for solutes of all length scales near hydrophobic surfaces. Further, the driving force for hydrophobically driven assembly in the vicinity of hydrophobic ...

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Section: Modelsmentioning

confidence: 58%

Extended surfaces modulate hydrophobic interactions of neighboring solutes

Patel

Varilly

Jamadagni

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

154

224

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“…Moreover, the introduction of greater spacing between proline residues correlated with the progressive retardation of droplet growth, consistent with more rapid loss of surface fluidity and stabilization of droplet surfaces, preventing coalescence (30,34). Growing evidence shows that water-hydrophobic interfaces promote the self-organization of amphipathic sequences into ␤-sheet structures (53)(54)(55). Thus, the presence of longer uninterrupted proline-free sequences in domain P6N could promote increased formation of ␤-structures at the interface of the colloidal droplets with water, contributing to surface stability and facilitating droplet clustering through direct interactions between ␤-structures.…”

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 78%

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Muiznieks

Keeley

2010

Journal of Biological Chemistry

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Elastin is a self-assembling protein of the extracellular matrix that provides tissues with elastic extensibility and recoil. The monomeric precursor, tropoelastin, is highly hydrophobic yet remains substantially disordered and flexible in solution, due in large part to a high combined threshold of proline and glycine residues within hydrophobic sequences. In fact, proline-poor elastin-like sequences are known to form amyloidlike fibrils, rich in ␤-structure, from solution. On this basis, it is clear that hydrophobic elastin sequences are in general optimized to avoid an amyloid fate. However, a small number of hydrophobic domains near the C terminus of tropoelastin are substantially depleted of proline residues. Here we investigated the specific contribution of proline number and spacing to the structure and self-assembly propensities of elastin-like polypeptides. Increasing the spacing between proline residues significantly decreased the ability of polypeptides to reversibly self-associate. Real-time imaging of the assembly process revealed the presence of smaller colloidal droplets that displayed enhanced propensity to cluster into dense networks. Structural characterization showed that these aggregates were enriched in ␤-structure but unable to bind thioflavin-T. These data strongly support a model where proline-poor regions of the elastin monomer provide a unique contribution to assembly and suggest a role for localized ␤-sheet in mediating self-assembly interactions.Elastin is the extracellular matrix protein responsible for the elasticity of vertebrate arterial vessels, connective tissues, lung, and skin. Elastin resilience is afforded by the formation of insoluble fibers, the first step of which involves the selfalignment of elastin monomers, tropoelastin, in a temperature-induced transition known as coacervation, through the association of hydrophobic domains (1, 2). Although highly (Ͼ75%) non-polar in character, tropoelastin remains predominantly monomeric and structurally disordered in solution (3-5) and critically, retains substantial backbone hydration and flexibility even when assembled (6) and cross-linked into mature, polymeric elastic arrays (7-13).Maintenance of structural heterogeneity and dynamics of the elastin backbone is achieved in large part by a high proportional composition of both proline (14%) and glycine (35%) residues within hydrophobic sequences (6, 14). These residues are commonly arranged into repeated motifs based on recurring sequence elements such as PGV and GVA. This includes a seven-fold tandem PGVGVA repeat in domain 24 of the native human elastin sequence (15). Contrary to enhancing coacervation or elastomeric properties, the multiple substitution of glycine residues for prolines within tandem repeat sequences (e.g. PGVGVA to GGVGVA) results in the formation of amyloid-like fibrils, rich in ␤-structure, from solution (6, 14). These structures are conformationally more restricted than native elastomeric sequences as a result of the tighter packing of residues into extended...

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“…This suggests that the β-amyloidlike fibrils can be formed more easily and rapidly by the self-assembly of the polypeptides on hydrophobic surfaces, especially for the short peptides. Experimental and simulation results have shown that the self-assembly of peptides can be highly accelerated on hydrophobic surfaces [36,37]. Thus, from an application viewpoint, the present study is helpful in developing more efficient strategies of producing high-quality biological fibrillar materials and functional nanoscale devices through the self-organization of polypeptides on the hydrophobic surfaces.…”

Section: Discussionmentioning

confidence: 89%

Effects of surface hydrophobicity on the conformational changes of polypeptides of different length

Yan

2011

Phys. Rev. E

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We studied the effects of surface hydrophobicity on the conformational changes of different length polypeptides by calculating the free energy difference between peptide structures using the bias-potential Monte Carlo technique and the probability ratio method. It was found that the hydrophobic surface plays an important role in the stability of secondary structures of the polypeptides with hydrophobic side chains. For short GAAAAG peptides, the hydrophobic surface destabilizes the α helix but stabilizes the β hairpin in the entire temperature region considered in our study. Interestingly, when the surface hydrophobic strength ε(hpsf)≥ε(hp), the most stable structure in the low temperature region changes from α helix to β hairpin, and the corresponding phase transition temperature increases slightly. For longer GAAAAAAAAAAG peptides, the effects of the relatively weak hydrophobic surface (ε(hpsf) < ε(hp)) on α-helical structures may be neglected, while the relatively strongly hydrophobic surface (ε(hpsf)≥ε(hp)) leads to the obvious partial helicity loss. In contrast, the stability of β structures can be enhanced significantly by the hydrophobic surface, especially by the strongly hydrophobic surface, at low and intermediate temperatures. At high temperatures, in addition to thermal fluctuations, the strongly hydrophobic surface (ε(hpsf)>ε(hp)) may further disturb the formation of both α-helical and β structures. Moreover, the phase transition temperature between α-helical structures and random coils significantly decreases due to the helicity loss when ε(hpsf)>ε(hp). Our findings provide a basic and quantitative picture for understanding the effects of a hydrophobic surface on the conformational changes of the polypeptides with hydrophobic side chains. From an application viewpoint, the present study is helpful in developing alternative strategies of producing high-quality biological fibrillar materials and functional nanoscale devices by the self-assembly of the polypeptides on hydrophobic surfaces.

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Molecular mechanism of β‐sheet self‐organization at water‐hydrophobic interfaces

Cited by 46 publications

References 108 publications

Extended surfaces modulate hydrophobic interactions of neighboring solutes

Extended surfaces modulate hydrophobic interactions of neighboring solutes

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Effects of surface hydrophobicity on the conformational changes of polypeptides of different length

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