| Popis: |
According to the Chou-Fasman rules for predicting the secondary structures of proteins, the 12–20 portion of salmon calcitonin should adopt an alpha helical conformation. These residues would form an amphipathic helix and contribute to the solubilization of certain phospholipids by the peptide. Circular dichroism was used to assess the extent that peptide segments of salmon calcitonin fold into structures of higher helical content in the presence of dimyristoylphospha-tidylglycerol, lysolecithin or sodium dodecyl sulfate. All of the segments studied are carboxyl terminal amides as is the native, intact, salmon calcitonin. Salmon calcitonin segments 11–23 or 12–23 form no more helical structure in the presence of lipids or detergents than does a segment comprising the hydro-philic carboxyl terminal residues 22–32 which is not predicted to adopt a helical conformation. Even a larger segment containing residues 12–32 does not exhibit a great increase in helical content in the presence of lipids or detergents, and it causes only a small broadening of the phase transition of dimyristoyl-phosphatidylglycerol. In contrast, a preparation with an equivalent molar ratio of dimyristoylphosphatidylglycerol to the salmon calcitonin segment 1–23 exhibits a very marked broadening of the phase transition, similar to what is found with the 32 amino acid native hormone. This amino terminal segment also adopts a conformation of higher helical content than even the intact hormone. This 1–23 segment is the only one studied that showed significant interaction with lipids, and it is also the only one which exhibited any hypocalcemic activity. The association constant for the binding of the 1–23 segment to dimyristoylphosphatidylglycerol is 2.4 × 104 M-1 compared with 1.0 × 105 M-1 for salmon calcitonin. The reduction in the affinity for lipid which occurs by removing residues 24–32 is much less than the reduction in biological activity. These and previous results indicate that the properties which give rise to lipid binding contribute to receptor affinity but are not the sole determining factor. |
