Bonding of molecular oxygen to T state human haemoglobin

Abstract

Haemoglobin (Hb) is the tetrameric protein molecule that in vertebrate blood transports oxygen from the lungs to the tissues. This function depends on four subuits in the molecule binding cooperatively so that their affinity for oxygen increases as the level of oxygenation increases. X-ray analysis has shown that deoxyhaemoglobin, which has a low oxygen affinity, and oxyhaemoglobin, which has a high oxygen affinity, differ principally in their summit or quaternary structures¹, referred to as the T and R states, respectively. As it switches from the T state to the R state during oxygenation, Hb increases its oxygen affinity. However, the structural pathway between deoxy- and oxyhaemoglobin is not known, principally because there has been no accurate structural knowledge of the intermediate states. We report here the crystal structure of T state human Hb in which the α chains are oxygenated and the β subunits are oxygen-free. In this crystal the Hb appears to be in an intermediate state between the unliganded T state and the liganded R state. There is also evidence that the Hb molecule operates by loading and unloading the β haems and thus the α-oxy,β-deoxy Hb crystal may represent a physiologically important state².