Insights into the Function of the Unstructured N-Terminal Domain of Proteins 4.1R and 4.1G in Erythropoiesis

Figure 6

Model proposed for Ca²⁺/CaM-dependent regulation of 4.1R binding to membrane proteins. Erythroblast intracellular Ca²⁺ concentration is normally maintained at less than 0.1 μM (10⁻⁷ M) [39, 40] (upper panel). At higher Ca²⁺ concentrations, CaM binds to the HP region. This results in a conformational and/or electric surface change which alters 4.1R binding sites, 4.1R¹³⁵ interacting consequently with lower affinity with its binding partner band 3 and no longer interacting with GPC, and p55. This model implies a Ca²⁺/CaM-dependent regulation of protein 4.1R binding to transmembrane proteins. Erythrocyte intracellular Ca²⁺ concentration is normally maintained at less than 1.0 μM (10⁻⁶ M) (lower panel). At this Ca²⁺ concentration, CaM is bound predominantly to the Ca²⁺-independent site located in peptide 11 of the 30 kDa domain (see [12, 38]). At higher Ca²⁺ concentrations, CaM-binding affinity for the Ca²⁺-dependent site, located in peptide 9 of the 30 kDa domain, increases. This results in a conformational and/or electric surface change which alters 4.1R binding sites, 4.1R interacting consequently with lower affinity with its binding partners p55, GPC, and spectrin/actin. This model implies that CaM regulates protein 4.1R binding to transmembrane proteins through Ca²⁺-independent and Ca²⁺-dependent binding sites.