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

The hemoglobin alpha-beta interface is a critical structural region within the heterotetrameric hemoglobin molecule, comprising the contact points between alpha and beta globin subunits. There are two primary interfaces: the alpha1-beta1 interface, which remains relatively stable, and the alpha1-beta2 interface, which undergoes significant sliding during the transition between the deoxygenated (T-state) and oxygenated (R-state) conformations (UniProt P69905; UniProt P68871). This allosteric transition is fundamental to the cooperative binding of oxygen, allowing hemoglobin to efficiently pick up oxygen in the lungs and release it in peripheral tissues (Oksenberg et al., 2016, doi:10.1111/bjh.14214). In sickle cell disease, a mutation in the beta-globin gene (HbS) causes the hemoglobin to polymerize when in the deoxygenated T-state, leading to red blood cell distortion, hemolysis, and vaso-occlusion (Vichinsky et al., 2019, doi:10.1056/NEJMoa1903212). Therapeutic agents like Voxelotor target this system by binding to the N-terminal valine of the alpha-globin chain, which allosterically stabilizes the R-state and increases oxygen affinity (FDA, 2019, Oxbryta Prescribing Information). By maintaining hemoglobin in its oxygenated form, these drugs prevent the T-state-dependent polymerization of HbS, thereby mitigating the clinical manifestations of sickle cell disease.

Other names

Hemoglobin alpha1-beta1 interfaceHemoglobin alpha1-beta2 interfaceHb alpha-beta contactHemoglobin tetramer interface

Allosteric stabilization of the oxygenated (R-state) hemoglobin tetramer, which increases oxygen affinity and prevents the polymerization of deoxygenated sickle hemoglobin (HbS).