Structure of liganded T-state haemoglobin from cat (Felis silvestris catus), a low oxygen-affinity species, in two different crystal forms

Haemoglobin (Hb) is an iron-containing metalloprotein which plays a major role in the transportation of oxygen from the lungs to tissues and of carbon dioxide back to the lungs. Hb is in equilibrium between low-affinity tense (T) and high-affinity relaxed (R) states associated with its unliganded and liganded forms, respectively. Mammalian species can be classified into two groups on the basis of whether they express 'high' or 'low' oxygen-affinity Hbs. Although Hbs from the former group have been studied extensively, a more limited number of structural studies have been performed for low oxygen-affinity Hbs. Here, the crystal structure of low oxygen-affinity cat methaemoglobin (metHb) has been solved at 2.0 and 2.4 Å resolution in two different crystal forms. Even though both structures are fully liganded, they unusually adopt a T-state-like quaternary conformation but with several localized R-like tertiary-structural and quaternary-structural features. The study provides atomic-level insights into the ligand-binding properties of this Hb, including its low cooperativity, blunt response to allosteric effectors and low affinity for oxygen, as well as further contributing to the mechanism underlying Hb allostery.