Cross-correlated chemical shift modulation: A signature of slow internal motions in proteins

A novel NMR experiment allows one to characterize slow motion in macromolecules. The method exploits the fact that motions, such as rotation about dihedral angles, induce correlated fluctuations of the isotropic chemical shifts of the nuclei in the vicinity. The relaxation of two-spin coherences involving C^α and C^β nuclei in proteins provides information about correlated fluctuations of the isotropic chemical shifts of C^α and C^β. The difference between the relaxation rates of double- and zero-quantum coherences C₊^α C₊^β and C₊^α C_-^β is shown to be affected by cross-correlated chemical shift modulation. In ubiquitin, evidence for slow motion is found in loops or near the ends of β-strands and α-helices.