Hémoglobines : structure et fonction

Human haemoglobin belongs to an ancient family of molecules that appeared some 1.8 milliard years ago. The structural feature, common to all the members of the globin family is a typical fold made by 6-8 helices surrounding the haeme group. In the vertebrates, the haemoglobin contained in the red blood cells is a heterotetramer that consists of two types of chains. Several regions of this molecule play key roles in oxygen binding; this is mainly the case of residues surrounding the haeme, of contact areas between chains, and of binding sites for regulatory ligands. In man several haemoglobins appear successively during ontogenic evolution and a different pattern of haemoglobins is present in the various periods of life. Reversible oxygen binding is the main function of haemoglobin: it results from equilibrium between two quaternary states: the first is a relaxed one, which displays a high oxygen affinity while the second is a tense one with low affinity. In this review we define the main parameters that describe oxygen binding and we report some models that show how they are interconnected. In the more recent models a predominant role is played by the binding of regulatory ligands and by the presence of hybrid or intermediary species. To date, site directed mutagenesis allows designing recombinant haemoglobins specially adapted to investigate the function of specific regions of the molecule and perhaps to offer new therapeutic approaches.