Transient protein–protein interactions visualized by solution NMR

Liu, Zhu; Gong, Zhou; Xu, Dongyan; Tang, Chun

doi:10.1016/j.bbapap.2015.04.009

Cited by 54 publications

(39 citation statements)

References 84 publications

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“…NMR spectroscopy is an established approach within drug discovery (Dias and Ciulli, 2014;van Dongen et al, 2002;Erlanson et al, 2016;Harner et al, 2013;Meyer and Peters, 2003) and molecular interactions (Collins et al, 2015;Liu et al, 2016;Williamson, 2013) due to its provision of detailed, spatial information on binding interfaces and in some cases ligand orientations . Here, the seminal publication by Shuker et al (1996) demonstrated the characterisation of structure-activity relationships based on observed chemical-shift perturbations (Williamson, 2013) on the receptor as caused by bound ligand.…”

Section: Nuclear Magnetic Resonancementioning

confidence: 99%

The role of small-angle scattering in structure-based screening applications

Chen

Hennig

2018

Biophys Rev

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In many biomolecular interactions, changes in the assembly states and structural conformations of participants can act as a complementary reporter of binding to functional and thermodynamic assays. This structural information is captured by a number of structural biology and biophysical techniques that are viable either as primary screens in small-scale applications or as secondary screens to complement higher throughput methods. In particular, small-angle X-ray scattering (SAXS) reports the average distance distribution between all atoms after orientational averaging. Such information is important when e.g. investigating conformational changes involved in inhibitory and regulatory mechanisms where binding events do not necessarily cause functional changes.Thus, we summarise here the current and prospective capabilities of SAXS-based screening in the context of other methods that yield structural information. Broad guidelines are also provided to assist readers in preparing screening protocols that are tailored to available X-ray sources.

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Section: Nuclear Magnetic Resonancementioning

confidence: 99%

The role of small-angle scattering in structure-based screening applications

Chen

Hennig

2018

Biophys Rev

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“…Paramagnetic relaxation enhancement (PRE) also provides long-range distance information between a covalently tagged paramagnetic probe and the nuclei of a biological macromolecule (Clore and Iwahara 2009). The PRE has been successfully used for proteins for the characterization of protein structure and dynamics (Liu et al 2014(Liu et al , 2015(Liu et al , 2016. Though the conjugation methods originated from electron paramagnetic resonance (EPR) and FRET (Edwards and Sigurdsson 2007;Zhang et al 2009), tagging an RNA with a paramagnetic probe remains technically challenging.…”

Section: Introductionmentioning

confidence: 99%

Refining RNA solution structures with the integrative use of label-free paramagnetic relaxation enhancement NMR

Gong

Yang

et al. 2019

Biophys Rep

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NMR structure calculation is inherently integrative, and can incorporate new experimental data as restraints. As RNAs have lower proton densities and are more conformational heterogenous than proteins, the refinement of RNA structures can benefit from additional types of restraints. Paramagnetic relaxation enhancement (PRE) provides distance information between a paramagnetic probe and protein or RNA nuclei. However, covalent conjugation of a paramagnetic probe is difficult for RNAs, thus limiting the use of PRE NMR for RNA structure characterization. Here, we show that the solvent PRE can be accurately measured for RNA labile imino protons, simply with the addition of an inert paramagnetic cosolute. Demonstrated on three RNAs that have increasingly complex topologies, we show that the incorporation of the solvent PRE restraints can significantly improve the precision and accuracy of RNA structures. Importantly, the solvent PRE data can be collected for RNAs without isotope enrichment. Thus, the solvent PRE method can work integratively with other biophysical techniques for better characterization of RNA structures.

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“…The challenge emerges because the dynamic ranges of most optical and biophysical methods are in the μ M –n M concentration interval, resulting in a decrease of sensitivity at lower concentrations and signal saturation at higher concentrations. Compared to most other methods, Nuclear Magnetic Resonance (NMR) spectroscopy stands out as the more versatile, since it is capable of providing quantitative information for protein–ligand interaction with affinities lower than μ M , even when these are ultra‐weak . Since NMR exploits the magnetic properties of the nuclei and thus measures properties of individual nuclei in a molecule, the method is also capable of separating signals from individual populations of molecules.…”

Section: Introductionmentioning

confidence: 99%

“…Compared to most other methods, Nuclear Magnetic Resonance (NMR) spectroscopy stands out as the more versatile, since it is capable of providing quantitative information for protein-ligand interaction with affinities lower than lM, even when these are ultra-weak. 10,11 Since NMR exploits the magnetic properties of the nuclei and thus measures properties of individual nuclei in a molecule, the method is also capable of separating signals from individual populations of molecules. Moreover, and importantly, the many diverse methods encountered by NMR spectroscopy makes it highly suitable for quantification of protein-ligand interactions, even at high concentrations.…”

Section: Introductionmentioning

confidence: 99%

(S)Pinning down protein interactions by NMR

et al. 2017

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Protein molecules are highly diverse communication platforms and their interaction repertoire stretches from atoms over small molecules such as sugars and lipids to macromolecules. An important route to understanding molecular communication is to quantitatively describe their interactions. These types of analyses determine the amounts and proportions of individual constituents that participate in a reaction as well as their rates of reactions and their thermodynamics. Although many different methods are available, there is currently no single method able to quantitatively capture and describe all types of protein reactions, which can span orders of magnitudes in affinities, reaction rates, and lifetimes of states. As the more versatile technique, solution NMR spectroscopy offers a remarkable catalogue of methods that can be successfully applied to the quantitative as well as qualitative descriptions of protein interactions. In this review we provide an easy‐access approach to NMR for the non‐NMR specialist and describe how and when solution state NMR spectroscopy is the method of choice for addressing protein ligand interaction. We describe very briefly the theoretical background and illustrate simple protein–ligand interactions as well as typical strategies for measuring binding constants using NMR spectroscopy. Finally, this review provides examples of caveats of the method as well as the options to improve the outcome of an NMR analysis of a protein interaction reaction.

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Transient protein–protein interactions visualized by solution NMR

Cited by 54 publications

References 84 publications

The role of small-angle scattering in structure-based screening applications

The role of small-angle scattering in structure-based screening applications

Refining RNA solution structures with the integrative use of label-free paramagnetic relaxation enhancement NMR

(S)Pinning down protein interactions by NMR

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