Molecular hinges in protein folding: the urea-denatured state of apomyoglobin

Unfolded apomyoglobin in 8 M urea at pH 2.3 displays distinct regions with different backbone mobility, as monitored by NMR relaxation. These variations in backbone mobility can be correlated with intrinsic properties of the amino acids in the sequence. Clusters of small amino acids such as glycine and alanine show increased backbone mobility compared to the average. In contrast, local hydrophobic interactions that persist in urea denaturant cause some restriction of backbone motions on a picosecond to nanosecond time scale. The model derived from the behavior of apoMb in urea depends only on the most fundamental properties of the local amino acid sequence, and thus provides a feasible paradigm for the initiation of folding.