Under physiological conditions intrinsically disordered proteins (IDPs) lack a rigid three-dimensional structure; they can be rather described as a large ensemble of possible structures, that are adopted only transiently . Nonetheless, in organisms they play a variety of roles, e.g. related to signaling and regulation. Interestingly, their flexibility is often crucial for fulfilling these functions. The fact that IDPs are very common, especially in eukaryotic organisms, and their relations to many human diseases, makes them an important object to study.
Due to their relation to backbone dihedral angles, cross-correlated relaxation (CCR) rates are a valuable source of information on protein structure . Such measurements are typically included in three-dimensional (3D) NMR experiments. CCR rates can be also studied for IDPs, where they report on the residual structure. Here, we present the new 4D experiment for the measurement of HNHα diople-dipole – C’ chemical shift anisotropy CCR rate. This rate offers interesting structural information.
The high dimensionality of the proposed experiment provides the resolution that enables efficient studies of IDPs. The inherent flexibility of IDPs causes their chemical shift range to be significantly narrower than in the case of folded proteins. In 3D spectra of an IDP the level of peak overlap can be substantial, limiting the amount of available information. To overcome this problem, the CCR rates measurements can be implemented into higher-dimensional experiments, where the peaks are distributed over a wider spectral space, thus decreasing the number of overlapping peaks .
To enable acquisition of high-dimensional data, non-uniform sampling was employed, and for processing a compressed sensing iterative soft thresholding algorithm  was used.
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