Folding studies on the human chorionic gonadotropin beta-subunit using optical spectroscopy of peptide fragments

Conformational preferences for the peptides SRPINATLAVEKEGSPVSITVNTTISA (H1 ) and APTMTRVLQGVLPALPQVVCNYR (H2) corresponding to the amino acid residues 9-35 and 38-60, respectively, of the glycoprotein hormone human chorionic gonadotropin beta-subunit (hCG beta) were studied by Fourier transform infr ared spectroscopy (FTIR) and vibrational and electronic circular dichroism (VCD and ECD) in various environments. These peptides correspond to the H1 (beta-like) and H2 (loop) hairpins of the native-state hCG beta subunit def ined by X-ray analysis. As demonstrated by FTIR and VCD, the H1 peptide ado pts a beta-structure in water as well as in environments that normally indu ce alpha-helix formation; Such as mixed trifluoroethanol/H2O solvent or mic ellar concentrations of sodium dodecyl sulfate. By contrast, the H2 peptide ECD and VCD spectra are consistent with a significant fraction of the resi dues being in either a poly-L-proline II like or a partially helical confor mation depending on the environment. A third peptide, H3, corresponding to the 60-87 hairpin region of hCG beta, which was studied previously, switche s its conformation depending on both the solvent and peptide concentration. Taken together, the data suggest that hCG beta may fold by, first, the H1 region rapidly adopting a beta-hairpin structure, followed by its hydrophob ic collapse with the H3 region, which in turn facilitates the formation of the H3 beta-hairpin. The H2 hairpin loop is formed as a result of the forma tion of the H1 and H3 beta-hairpin interactions.