Supplementary Figure 4: Impact of the mutation p.Asp70Asn in EPO.

(a) Crystal structure of erythropoietin (EPO, yellow) with two erythropoietin receptor subunits (EPOR, green and red)²⁴. The white circle indicates the interface between EPO and EPOR magnified in (b) and (c). In (b) and (c), the white circles highlight residue 70 (43 after cleavage of the propeptide). Replacing Asp70 (b) by Asn70 (c) may destabilize the EPO loop that interacts with EPOR because it disrupts a hydrogen bond between Asp70 and Thr71.