EPR in Protein Science

Drescher, Malte

doi:10.1007/128_2011_235

Cited by 69 publications

(46 citation statements)

References 144 publications

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“…25 In contrast, globular proteins frequently display DEER time traces with significant and apparent dipolar modulations because their narrow conformational ensembles give rise to a restricted interspin distance range (see Figure S1b of the Supporting Information for time traces calculated from a single discrete interspin distance). 21 Because the established standard analysis methods 26 cannot be applied for the nonmodulated DEER data under investigation, we analyze DEER time traces through an effective modulation depth, Δ eff (as sketched in Figure 2 and Figure S1b of the Supporting Information), which denotes the total signal decay at a t max of 3 μs. As such, Δ eff = 1 – V ( t = 3 μs)/ V ( t = 0).…”

Section: Resultsmentioning

confidence: 99%

Cooperative Unfolding of Compact Conformations of the Intrinsically Disordered Protein Osteopontin

et al. 2013

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Intrinsically disordered proteins (IDPs) constitute a class of biologically active proteins that lack defined tertiary and often secondary structure. The IDP Osteopontin (OPN), a cytokine involved in metastasis of several types of cancer, is shown to simultaneously sample extended, random coil-like conformations and stable, cooperatively folded conformations. By a combination of two magnetic resonance methods, electron paramagnetic resonance and nuclear magnetic resonance spectroscopy, we demonstrate that the OPN ensemble exhibits not only characteristics of an extended and flexible polypeptide, as expected for an IDP, but also simultaneously those of globular proteins, in particular sigmoidal structural denaturation profiles. Both types of states, extended and cooperatively folded, are populated simultaneously by OPN in its apo state. The heterogeneity of the structural properties of IDPs is thus shown to even involve cooperative folding and unfolding events.

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Section: Resultsmentioning

confidence: 99%

Cooperative Unfolding of Compact Conformations of the Intrinsically Disordered Protein Osteopontin

et al. 2013

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“…These types of measurements are highly useful in describing local and/or short-range interactions of the bound and free IDP state, while global descriptors of order/disorder are usefully defined through SAXS or SANS experiments for categorization of a free IDP into collapsed semi-ordered ensembles, collapsed disordered ensembles, or extended disordered ensembles 1,2,4,50 , based on the distribution of heavy atom distances. Additional NMR and ESR experiments such as through-space dipole-dipole interactions that give rise to the Nuclear Overhauser Effect (NOE), and paramagnetic relaxation enhancements (PRE) from an attached spin label 71 , as well as the more recent EPR 72 and DEER 73 experiments, are in principle information-rich since they report on both local and non-local tertiary structure contacts that would be valuable in restraining the IDP ensemble.…”

Section: Experimental Methods and Future Innovationsmentioning

confidence: 99%

Finding Our Way in the Dark Proteome

Bhowmick¹,

Brookes²,

Yost³

et al. 2016

J. Am. Chem. Soc.

115

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The traditional structure-function paradigm has provided significant insights for well-folded proteins in which structures can be easily and rapidly revealed by X-ray crystallography beamlines. However approximately one third of the human proteome are comprised of intrinsically disordered proteins and regions (IDPs/IDRs) that do not adopt a dominant well-folded structure, and therefore remain “unseen” by traditional structural biology methods. This Perspective article considers the challenges raised by the “Dark Proteome”, in which determining the diverse conformational substates of IDPs in their free states, in encounter complexes of bound states, and in complexes retaining significant disorder, requires an unprecedented level of integration of multiple and complementary solution-based experiments that are analyzed with state-of-the art molecular simulation, Bayesian probabilistic models, and high throughput computation. We envision how these diverse experimental and computational tools can work together through formation of a “computational beamline” that will allow key functional features to be identified in IDP structural ensembles.

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“…For both mfp-3S-pepSL and mfp3F-pepSL, the EPR spectra before the corresponding coacervate formation consisted of a single spectral component (Figure S3a and S3b), displaying high mobility ( τ rot ≈ 0.1 ns) as typically observed for unstructured peptides in solution state 36 . Upon coacervate formation, a second “slow” spectral component appears (Figure S4a and S4b) that corresponds to a peptide population with restricted rotational mobility of its spin label.…”

Section: Resultsmentioning

confidence: 72%

Simple peptide coacervates adapted for rapid pressure-sensitive wet adhesion

et al. 2017

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We report here that a dense liquid formed by spontaneous condensation, also known as simple coacervation, of a single-component mussel foot protein-3S-mimicking peptide exhibits properties critical for underwater adhesion. A structurally homogeneous coacervate is deposited on underwater surfaces as micrometer-thick layers, and, after compression, displays orders of magnitude higher underwater adhesion at 2 N/m than that reported from thin films of the most adhesive mussel-foot-derived peptides or their synthetic mimics. The increase in adhesion efficiency does not require nor rely on post-deposition curing or chemical processing, but rather represents an intrinsic physical property of the coacervate. Its wet adhesive and rheological properties correlate with significant dehydration, tight peptide packing and restriction in peptide mobility. We suggest that such dense coacervate liquids represent an essential adaptation for the initial priming stages of mussel adhesive deposition, and provide a hitherto untapped design principle for synthetic underwater adhesives.

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EPR in Protein Science

Cited by 69 publications

References 144 publications

Cooperative Unfolding of Compact Conformations of the Intrinsically Disordered Protein Osteopontin

Cooperative Unfolding of Compact Conformations of the Intrinsically Disordered Protein Osteopontin

Finding Our Way in the Dark Proteome

Simple peptide coacervates adapted for rapid pressure-sensitive wet adhesion

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