Conformational properties of the isolated 1-23 fragment of human hemoglobin alpha-chain

With the purpose of establishing whether, as a general rule, regions of a protein chain that are helical in the native structure maintain, at least partially, the same helical structure when isolated in solution, we have prepared the 1-23 fragment of human hemoglobin alpha-chain, and studied its conformational properties in aqueous solution by CD and 1H-NMR. From the analysis of CD and NMR spectral changes with temperature, salt and addition of trifluoroethanol (TFE) it can be concluded that the 1-23 peptide forms a measurable population (18% at 22 degrees C (pH 5.6) TFE/H2O, 30:70 (v/v)) of an alpha-helix structure that spans the same residues that are helical in the native protein (namely, 6 to 17). These results, taken together with similar ones obtained previously in the 1-19, 21-42 and 50-61 RNAase fragments, support the idea that no helices other than the native ones are actually formed in solution by protein fragments. This implies that the final helical structure of a protein is present from the very beginning of the folding process, and also that such elements of secondary structure can act as primary nucleation centers.