Prediction of the secondary and tertiary structures of interferon from four homologous amino acid sequences

The secondary and tertiary structures of interferon were predicted from four homologous amino acid sequences. Three methods of secondary structure prediction gave differing results that were interpreted to suggest that there might be four α-helices that are important in the tertiary fold. The validity of this interpretation was assessed by the application of the methods to predict the secondary structures of two proteins known to consist of four α-helices. A possible tertiary model for interferon is then proposed in which the four α-helices pack into a right-handed bundle similar to that observed in several known protein structures. This model was shown to be stereochemically feasible by an α-helix docking algorithm. One of the resultant structures is shown to be compatible with the known disulphide linkages in interferon. Certain residues that are conserved between the different sequences lie near each other in our model and these residues might form a functional site. In the absence of a crystal structure for interferon, a predicted tertiary model will help further structural and functional studies.