Hemoglobin subunit alpha-beta interface (Hb alpha-beta interface)

The hemoglobin alpha-beta interface is a critical structural domain within the hemoglobin heterotetramer, which is composed of two alpha and two beta subunits. This interface is essential for the allosteric regulation of oxygen binding, mediating the transition between the T (tense, low-affinity) and R (relaxed, high-affinity) conformational states (Perutz, M. F., Nature, 1970). In sickle cell disease, the deoxygenated T-state of hemoglobin S (HbS) is susceptible to polymerization, which causes red blood cells to sickle and leads to vaso-occlusive crises and hemolysis (Eaton, W. A., & Bunn, H. F., Blood, 2017). Therapeutic agents such as Voxelotor target the alpha-globin subunits near this interface to stabilize the R-state, thereby increasing the overall oxygen affinity of the hemoglobin molecule (Vichinsky, E. P., et al., New England Journal of Medicine, 2019). By maintaining hemoglobin in its oxygenated form, these drugs effectively reduce the concentration of deoxygenated HbS available for polymerization. Consequently, the alpha-beta interface serves as a vital pharmacological target for modulating hemoglobin's physical properties to treat various hemoglobinopathies (UniProt, P69905).

Other names

alpha1-beta1 interfacealpha1-beta2 interfaceHemoglobin dimer interfaceHb alpha-beta contactHemoglobin subunit alpha-beta protein-protein interaction site

Allosteric stabilization of the high-oxygen-affinity (R) state of hemoglobin, which shifts the oxygen-hemoglobin dissociation curve to the left and prevents the polymerization of deoxygenated sickle hemoglobin (HbS).