With the development of NMR methodology and technology during the past decades, solid-state NMR (ssNMR) has become a particularly important tool for investigating structure and dynamics at atomic scale in biological systems, where the recoupling techniques play pivotal roles in modern high-resolution MAS NMR. In this review, following a brief introduction on the basic theory of recoupling in ssNMR, we highlight the recent advances in dipolar and chemical shift anisotropy recoupling methods, as well as their applications in structural determination and dynamical characterization at multiple time scales (i.e., fast-, intermediate-, and slow-motion). The performances of these prevalent recoupling techniques are compared and discussed in multiple aspects, together with the representative applications in biomolecules. Given the recent emerging advances in NMR technology, new challenges for recoupling methodology development and potential opportunities for biological systems are also discussed.
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http://dx.doi.org/10.1021/acs.chemrev.1c00779 | DOI Listing |
Front Physiol
December 2024
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Introduction: Adrenergic activation of protein kinase A (PKA) in cardiac muscle targets the sarcolemma, sarcoplasmic reticulum, and contractile apparatus to increase contractile force and heart rate. In the thin filaments of the contractile apparatus, cardiac troponin I (cTnI) Ser22 and Ser23 in the cardiac-specific N-terminal peptide (NcTnI: residues 1 to 32) are the targets for PKA phosphorylation. Phosphorylation causes a 2-3 fold decrease of affinity of cTn for Ca associated with a higher rate of Ca dissociation from cTnC leading to a faster relaxation rate of the cardiac muscle (lusitropy).
View Article and Find Full Text PDFBiophys J
January 2025
Departement of Chemistry, Université du Québec à Montréal, Montreal, Québec, Canada. Electronic address:
Fluorine-19 is an ideal nucleus for studying biological systems using NMR due to its rarity in biological environments and its favorable magnetic properties. In this work, we used a mixture of monofluorinated palmitic acids (PAs) as tracers to investigate the molecular interaction of the fluorinated drug rosuvastatin in model lipid membranes. More specifically, PAs labeled at the fourth and eighth carbon positions of their acyl chains were coincorporated in phospholipid bilayers to probe different depths of the hydrophobic core.
View Article and Find Full Text PDFChem Rev
November 2024
Department of Chemistry and Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Magic angle spinning (MAS) nuclear magnetic resonance (NMR) has evolved significantly over the past three decades and established itself as a vital tool for the structural analysis of biological macromolecules and materials. This review delves into the development and application of dipolar recoupling techniques in MAS NMR, which are crucial for obtaining detailed structural and dynamic information. We discuss a variety of homonuclear and heteronuclear recoupling methods which are essential for measuring spatial restraints and explain in detail the spin dynamics that these sequences generate.
View Article and Find Full Text PDFJ Phys Chem Lett
November 2024
Interdisciplinary Institute of NMR and Molecular Sciences, School of Chemistry and Chemical Engineering, State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.
Solid-state nuclear magnetic resonance (ssNMR) is indispensable for studying the structures, dynamics, and interactions of insoluble proteins in native or native-like environments. While ssNMR includes numerous nonselective techniques for general analysis, it also provides various selective methods that allow for the extraction of precise details about proteins. This perspective highlights three key aspects of selective methods: selective signals of protein segments, selective recoupling, and site-specific insights into proteins.
View Article and Find Full Text PDFJ Magn Reson
November 2024
Department of Chemistry and Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. Electronic address:
In magic angle spinning (MAS) experiments involving uniformly C/N labeled proteins, C-C and C-N dipolar recoupling experiments are now routinely used to measure direct dipole-dipole couplings that constrain distances and torsion angles and determine molecular structures. When the distances are short (<4 Å), the direct couplings dominate the evolution of the spin system, and the C-C and C-N J-couplings (scalar couplings) are ignored. However, for structurally interesting >4 Å distances, the dipolar and J-couplings are generally of comparable magnitude, and the variation in J must be included in order to optimize the precision of the experiment.
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