In our search for potential folding intermediates we have prepared and characterized the fragment of RNase A corresponding to residues 50–61. Proton chemical shift variations with temperature, addition of stabilizing (TFE) or denaturing agents (urea) provide a strong experimental basis for concluding that in aqueous solution this RNase fragment forms an α-helix structure similar to that in the intact RNase A crystal. This conclusion lends strong support to the idea that elements of secondary structure (mainly α-helices) can be formed in the absence of tertiary interactions and act as nucleation centers in the protein folding process.
