Environmental effects on the folding of functional peptide segments from steroid hormone receptors.

Recent improvements in circular dichroism (CD) instrumentation now allow investigators to obtain highly reliable and reproducible CD spectra in the far-UV range to near 180 nm. These advances, coupled with new computer software for spectral interpretation, allow accurate calculations of secondary structural content in proteins and polypeptides. CD is particularly reliable for the calculation of alpha-helical content. We have utilized these features to determine the propensity of alpha-helix formation in highly purified synthetic peptides corresponding to segments from proteins. We obtain CD spectra of the peptides in 90% 2,2,2-trifluoroethanol (90% TFE; an alpha-helix promoting solvent) and in 2 mM sodium dodecyl sulfate (2 mM SDS; a beta-sheet promoting solvent) to assess helix stability in these different chemical environments. Using this methodology, we demonstrate that a peptide corresponding to a biologically active segment of the human estrogen receptor forms a stable alpha-helix in both environments. In contrast, peptide segments of equal length from other steroid receptors are alpha-helical in TFE but not in 2 mM SDS. These results show that the conformation of a peptide is a function of both its amino acid sequence and the local chemical environment.