[NMR paper] NMR Methods to Dissect the Molecular Mechanisms of Disease-Related Mutations (DRMs): Understanding How DRMs Remodel Functional Free Energy Landscapes.
Related ArticlesNMR Methods to Dissect the Molecular Mechanisms of Disease-Related Mutations (DRMs): Understanding How DRMs Remodel Functional Free Energy Landscapes.
Methods. 2018 May 29;:
Authors: Byun JA, Melacini G
Abstract
Elucidating the molecular mechanism of disease-related mutations (DRMs) is a critical first step towards understanding the etiology of genetic disorders. DRMs often modulate biological function by altering the free-energy landscape (FEL) of the protein associated with the mutated gene. FELs typically include ground, as well as excited, yet accessible and functionally relevant, states and DRMs may perturb both the thermodynamics and kinetics of the ground vs. excited and apo vs. holo transitions. NMR is ideally suited to map at atomic-resolution these DRM-induced FEL perturbations. Here, we discuss NMR methods that can elucidate how DRMs remodel regulatory FELs by focusing on a simple, but prototypical, four-state allosteric FEL model. The approaches include the CHEmical Shift Projection Analysis, NMR spin relaxation measurements, and NMR measurements of effector-binding thermodynamics and kinetics. Together, these complementary NMR measurements provide a valuable picture of how DRMs modulate distinct FEL attributes that are critical for dissecting the molecular mechanisms underlying pathological phenotypes.
PMID: 29857190 [PubMed - as supplied by publisher]
Understanding 'disease mechanisms' of ALS - Science Daily
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Understanding 'disease mechanisms' of ALS
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Ubiquitin and UBQLN2 are part of what of Castaneda calls a "quality-control mechanism," which maintains proteins at their proper levels during the lifespan of a cell. (Unlike other cells, which live several days or weeks, neurons typically last an ...
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[NMR paper] Understanding the Effect of Disease-Related Mutations on Human Prion Protein Structure: Insights From NMR Spectroscopy.
Understanding the Effect of Disease-Related Mutations on Human Prion Protein Structure: Insights From NMR Spectroscopy.
Related Articles Understanding the Effect of Disease-Related Mutations on Human Prion Protein Structure: Insights From NMR Spectroscopy.
Prog Mol Biol Transl Sci. 2017;150:83-103
Authors: Biljan I, Ilc G, Plavec J
Abstract
Prion diseases or transmissible spongiform encephalopathies constitute a group of fatal neurodegenerative diseases that can be of sporadic, genetic, or acquired origin. The central...
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[NMR paper] Cell-free expression of the APP transmembrane fragments with Alzheimer's disease mutations using algal amino acid mixture for structural NMR studies.
Cell-free expression of the APP transmembrane fragments with Alzheimer's disease mutations using algal amino acid mixture for structural NMR studies.
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Protein Expr Purif. 2016 Apr 9;
Authors: Bocharova OV, Urban AS, Nadezhdin KD, Bocharov EV, Arseniev AS
Abstract
Structural investigations need ready supply of the isotope labeled proteins with inserted mutations n the...
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Study finding could shed light on molecular mechanisms underlying Huntington's disease - News-Medical.net
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Study finding could shed light on molecular mechanisms underlying Huntington's disease
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... the process," he said. "Using advanced nuclear magnetic resonance spectroscopy, we were able to provide an unprecedented view of the internal structure of the protein clumps that form in the disease, which we hope will one day lead to new therapies ...
Researchers Describe Brain Plaques Involved In...
[NMR paper] Mapping Protein Conformational Energy Landscapes Using NMR and Molecular Simulation.
Mapping Protein Conformational Energy Landscapes Using NMR and Molecular Simulation.
Mapping Protein Conformational Energy Landscapes Using NMR and Molecular Simulation.
Chemphyschem. 2013 May 23;
Authors: Guerry P, Mollica L, Blackledge M
Abstract
Nuclear magnetic resonance (NMR) spectroscopy provides detailed understanding of the nature and extent of protein dynamics on physiologically important timescales. We present recent advances in the combination of NMR with state-of-the-art molecular simulation that are providing unique new...
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[NMR paper] Characterization of the free-energy landscapes of proteins by NMR-guided metadynamics.
Characterization of the free-energy landscapes of proteins by NMR-guided metadynamics.
Related Articles Characterization of the free-energy landscapes of proteins by NMR-guided metadynamics.
Proc Natl Acad Sci U S A. 2013 Apr 9;
Authors: Granata D, Camilloni C, Vendruscolo M, Laio A
Abstract
The use of free-energy landscapes rationalizes a wide range of aspects of protein behavior by providing a clear illustration of the different states accessible to these molecules, as well as of their populations and pathways of interconversion. The...
NMR Methods to Dissect the Molecular Mechanisms of Disease-Related Mutations (DRMs): Understanding How DRMs Remodel Functional Free Energy Landscapes.
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