The Croonian Lecture, 1968 - The haemoglobin molecule

Haemoglobin is the respiratory protein of the red blood cells which carries oxygen from the lungs to the tissues and facilitates, both directly and indirectly, the return transport of carbon dioxide. Mammalian haemoglobin has a molecular weight of 64500 and contains two pairs of polypeptide chains: the α-chains with 141 amino acid residues each and the β-chains with 146. Each chain is combined with one haem. Myoglobin, the oxygen carrier of muscle, is closely related to haemoglobin, but has a simpler constitution: it consists of only one polypeptide chain of 153 residues and a single haem. The amino acid sequences of the myoglobins and haemoglobins of man and of several animals have been determined (Dayhoff & Eck 1968). By means of the method of isomorphous replacement with heavy atoms, X-ray analysis of sperm whale myoglobin at 2·0 Å resolution provided the first solution of the structure of a protein (Kendrew et al. 1960; Watson 1969). All but 21 of its 153 residues form part of helices; over most of their length these helices have conformations closely resembling the right-handed α-helix of Pauling & Corey (1951). The chain is divided into 8 helical segments, separated by corners or non-helical regions. Together these form a kind of basket into which the haem group fits neatly, so that only its propionic acid side-chains protrude into the surrounding liquid (figures 1, 2). X-ray analysis at 5·5 Å resolution showed each chain of horse haemoglobin to be folded in much the same way as the single chain of sperm whale myoglobin. The 4 chains are arranged tetrahedrally, each carrying one haem in a pocket near the protein surface. The chemically identical halves of the molecule are related by a twofold symmetry axis (figure 3, plate 18; Cullis et al. 1962).