Structure and function of haemoglobin: II. Some relations between polypeptide chain configuration and amino acid sequence

Abstract

X-Ray data suggest that the globin chain has the same configuration in the myoglobins and haemoglobins of all vertebrates. Sequence data, on the other hand, show that only 9 out of more than 140 sites are occupied by the same amino acid residue in all the globin chains analysed so far. The different globins do not have any marked pattern of ionized or of polar residues in common. The most prominent common feature is the almost total exclusion of polar residues from the interior of the globin chains; this expresses itself in a pattern of 30 sites where only non-polar residues occur. Along α -helical segments these invariant non-polar sites tend to repeat on the average at regular intervals of about 3·6 residues, making the interior face of the helix non-polar. At most sites at the surface or in surface crevices, on the other hand, replacements of many different kinds seem to occur without affecting the tertiary structure: these include replacement of non-polar by polar residues and vice versa . Prolines are confined to the ends of helices or to non-helical regions; otherwise their incidence in the globins of different species is largely random. If all the proline sites observed are plotted along the sequence, they are seen to place limits on the possible lengths of helical regions. In many instances, serine, threonine, aspartic acid or asparagine occupies the first site at the amino end of the helix, followed by a proline at the second site. In a protein of unknown structure, a regular periodicity of invariant non-polar sites might serve to recognize helical regions, and the incidence of prolines to define their lengths. A common pattern of non-polar sites might also help to identify structurally similar proteins with different enzymic function.