Dataset Information

Aromatic 19F-13C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics.

ABSTRACT: Atomic-level information about the structure and dynamics of biomolecules is critical for an understanding of their function. Nuclear magnetic resonance (NMR) spectroscopy provides unique insights into the dynamic nature of biomolecules and their interactions, capturing transient conformers and their features. However, relaxation-induced line broadening and signal overlap make it challenging to apply NMR spectroscopy to large biological systems. Here we took advantage of the high sensitivity and broad chemical shift range of 19F nuclei and leveraged the remarkable relaxation properties of the aromatic 19F-13C spin pair to disperse 19F resonances in a two-dimensional transverse relaxation-optimized spectroscopy spectrum. We demonstrate the application of 19F-13C transverse relaxation-optimized spectroscopy to investigate proteins and nucleic acids. This experiment expands the scope of 19F NMR in the study of the structure, dynamics, and function of large and complex biological systems and provides a powerful background-free NMR probe.

SUBMITTER: Boeszoermenyi A

PROVIDER: S-EPMC6549241 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Aromatic <sup>19</sup>F-<sup>13</sup>C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics.

Boeszoermenyi Andras A Chhabra Sandeep S Dubey Abhinav A Radeva Denitsa L DL Burdzhiev Nikola T NT Chanev Christo D CD Petrov Ognyan I OI Gelev Vladimir M VM Zhang Meng M Anklin Clemens C Kovacs Helena H Wagner Gerhard G Kuprov Ilya I Takeuchi Koh K Arthanari Haribabu H

Nature methods 20190311 4

Atomic-level information about the structure and dynamics of biomolecules is critical for an understanding of their function. Nuclear magnetic resonance (NMR) spectroscopy provides unique insights into the dynamic nature of biomolecules and their interactions, capturing transient conformers and their features. However, relaxation-induced line broadening and signal overlap make it challenging to apply NMR spectroscopy to large biological systems. Here we took advantage of the high sensitivity and ...[more]

PMID: 30858598

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Project description:Infrared (IR) spectroscopy has provided considerable insight into the structures, dynamics, and formation mechanisms of amyloid fibrils. IR probes, such as main chain 13C═18O, have been widely employed to obtain site-specific structural information, yet only secondary structures and strand-to-strand arrangements can be probed. Very few nonperturbative IR probes are available to report on the side-chain conformation and environments, which are critical to determining sheet-to-sheet arrangements in steric zippers within amyloids. Polar residues, such as glutamine, contribute significantly to the stability of amyloids and thus are frequently found in core regions of amyloid peptides/proteins. Furthermore, polyglutamine (polyQ) repeats form toxic aggregates in several neurodegenerative diseases. Here we report the synthesis and application of a new nonperturbative IR probe-glutamine side chain 13C═18O. We use side chain 13C═18O labeling and isotope dilution to detect the presence of intermolecularly hydrogen-bonded arrays of glutamine side chains (Gln ladders) in amyloid-forming peptides. Moreover, the line width of the 13C═18O peak is highly sensitive to its local hydration environment. The IR data from side chain labeling allows us to unambiguously determine the sheet-to-sheet arrangement in a short amyloid-forming peptide, GNNQQNY, providing insight that was otherwise inaccessible through main chain labeling. With several different fibril samples, we also show the versatility of this IR probe in studying the structures and aggregation kinetics of amyloids. Finally, we demonstrate the capability of modeling amyloid structures with IR data using the integrative modeling platform (IMP) and the potential of integrating IR with other biophysical methods for more accurate structural modeling. Together, we believe that side chain 13C═18O will complement main chain isotope labeling in future IR studies of amyloids and integrative modeling using IR data will significantly expand the power of IR spectroscopy to elucidate amyloid assemblies.

Dataset Information

Aromatic 19F-13C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics.

Publications

Aromatic <sup>19</sup>F-<sup>13</sup>C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics.

Similar Datasets

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