A Structure-free Method for Quantifying Conformational Flexibility in proteins

Burger, Virginia M.; Arenas, Daniel J.; Stultz, Collin M.

doi:10.1038/srep29040

Cited by 67 publications

(65 citation statements)

References 60 publications

(87 reference statements)

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“…To quantify the difference in conformational entropy of the peptide chains in solution and in the aggregate, we compared the ensembles in terms of their RgD entropy, a metric recently introduced by Burger et al to quantify the entropy of IDP ensembles. 33 The RgD entropy of aggregated chains (2.254) is 25% higher than that of the solution ensemble (1.808) ( Fig. S8), indicating a significant increase of conformational entropy upon aggregation.…”

Section: Peptide Chain Dimensions Before and After Self-assemblymentioning

confidence: 94%

The Liquid Structure of Elastin

Rauscher

Pomès

2016

Preprint

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The protein elastin imparts extensibility, elastic recoil, and resilience to tissues including arterial walls, skin, lung alveoli, and the uterus. Elastin and elastin-like peptides are hydrophobic, disordered, and undergo liquid-liquid phase separation upon self-assembly. Despite extensive study, the structure of elastin remains controversial. We use molecular dynamics simulations on a massive scale to elucidate the structural ensemble of aggregated elastin-like peptides. Consistent with the entropic nature of elastic recoil, the aggregated state is stabilized by the hydrophobic effect. However, self-assembly does not entail formation of a hydrophobic core. The polypeptide backbone forms transient, sparse hydrogen-bonded turns and remains significantly hydrated even as self-assembly triples the extent of non-polar side chain contacts. Individual chains in the assembly approach a maximally-disordered, melt-like state which may be called the liquid state of proteins. These findings resolve long-standing controversies regarding elastin structure and function and afford insight into the phase separation of disordered proteins.

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Section: Peptide Chain Dimensions Before and After Self-assemblymentioning

confidence: 94%

The Liquid Structure of Elastin

Rauscher

Pomès

2016

Preprint

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“…By contrast, the plots for the DBL3x-DBL6ε and DBL4ε-DBL6ε contain peaks that are shifted to longer qRg (1.8-1.95), indicative of a more elongated molecule. In addition, the plots for DBL3x-DBL6ε and DBL4ε-DBL6ε contain a shoulder at qRg ~4.9 and qRg ~4 respectively, and return to zero at qRg ~10, characteristic of proteins containing spatially distinct modules (54).…”

Section: Saxs Analysis Suggests That the Var2csa Ectodomain Is Compactmentioning

confidence: 98%

Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for receptor binding

Bewley

Gautam

Gowda

et al. 2020

Preprint

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VAR2CSA is the placental-malaria specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum infected host red blood cells and binds to specific chondroitin-4-sulfate (CSA) chains of the placental proteoglycan receptor. The functional ~310 kDa ectodomain of VAR2CSA is a multi-domain protein that requires a minimum 12-mer CSA molecule for specific, high affinity receptor binding. However, how these domains interact to create the receptor binding surface is not known, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative location of the domains creates two distinct pores that can each accommodate the 12-mer of CSA, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of IRBCs and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria.

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“…It has been observed that, for compact and globular (i.e., spherical) proteins, the variation of k 2 I c (k) with k is distinctly different and stronger than for ones in the partially disordered and/or unfolded states. 69,70 Specifically, a globular protein in the folded state exhibits an approximate semi-circular variation of k 2 I c (k) with k, which gradually dissipates or flattens out as the degree of structural disorder increases and the protein becomes partially disordered by unfolding itself. Following this observation, one may expect that the shape-dependence of the scattering intensity on a Kratky plot would be more pronounced for spherical voids than that for long cylindrical or highly elongated ellipsoidal voids (see Refs.…”

Section: Effect Of Void Shapes On Saxs: Kratky Plots For A-simentioning

confidence: 99%

Small-angle x-ray scattering in amorphous silicon: A computational study

Paudel¹,

Atta‐Fynn²,

Drabold³

et al. 2018

Phys. Rev. B

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We present a computational study of small-angle X-ray scattering (SAXS) in amorphous silicon (a-Si) with particular emphasis on the morphology and microstructure of voids. The relationship between the scattering intensity in SAXS and the three-dimensional structure of nanoscale inhomogeneities or voids is addressed by generating ultra-large high-quality a-Si networks with 0.1-0.3 % volume concentration of voids, as observed in experiments using SAXS and positron annihilation spectroscopy. A systematic study of the variation of the scattering intensity in the small-angle scattering region with the size, shape, number density, and the spatial distribution of the voids in the networks is presented. Our results suggest that the scattering intensity in the small-angle region is particularly sensitive to the size and the total volume-fraction of the voids, but the effect of the geometry or shape of the voids is less pronounced in the intensity profiles. A comparison of the average size of the voids obtained from the simulated values of the intensity, using the Guinier approximation and Kratky plots, with those from the spatial distribution of the atoms in the vicinity of void surfaces is presented.

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A Structure-free Method for Quantifying Conformational Flexibility in proteins

Cited by 67 publications

References 60 publications

The Liquid Structure of Elastin

The Liquid Structure of Elastin

Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for receptor binding

Small-angle x-ray scattering in amorphous silicon: A computational study

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