Understanding the conformational dynamics of proteins is essential to understanding their function at the molecular level.
The movements of individual atoms within a protein can be precisely quantified using NMR relaxation rates, but their measurement requires well-resolved spectral responses. Correlation spectra1H-15Two-dimensional N-scans are the standard approach for resolving amide signals in protein NMR, but they result in excessive experimental time costs when spectra are heavily crowded due to limited chemical shift dispersions 15N. This limitation often prevents the characterization of the dynamics of intrinsically disordered proteins, particularly when they exhibit regions of low complexity or homopolymers, or when the lifetime of the samples is short.
In this work conducted on the Lille NMR platformWe present a 1D NMR method 1H-15Fast and ultra-selective N-wavelength measurement that enables high-quality measurement of spin relaxation constants 15Individual N, even when the resonances 15N are spaced only 6 to 8 Hz apart. We demonstrate the new experiment by characterizing, for the first time, the pico- to nanosecond dynamics along a 16-residue polyglutamine segment in the huntingtin protein, the causative agent of Huntington's disease, as well as the millisecond conformational exchange in the SH3GL3 protein. This new experiment will find numerous applications in the study of the conformational dynamics of intrinsically disordered proteins or any other biomacromolecule exhibiting 2D spectra. 1H-15very dense N.
Article: https://pubmed.ncbi.nlm.nih.gov/41703747/
