Figure 5. A pathological erythropoietin (EPO) mutant with altered binding kinetics to EPO receptor (EPOR) causes qualitative changes in downstream signaling.

A homozygous p.R150Q EPO mutation was discovered in a patient with severe anemia caused by pure red cell aplasia (Diamond–Blackfan anemia). High levels of the mutant EPO failed to restore erythropoiesis despite an only threefold reduction in its overall affinity for EPOR. Compared with wild-type EPO, the mutant EPO interaction with EPOR was kinetically biased with higher on- and off-rates that altered the activation of specific EPOR effector pathways. k _on, rate of association; k _off, rate of dissociation. This figure was created using data from Kim et al. 2017 ¹³³.