Fig. 5 | Nature Communications

Fig. 5

From: Identification of rare sequence variation underlying heritable pulmonary arterial hypertension

Fig. 5

Structural analysis of GDF2 mutations. a Schematic diagram of GDF2 processing. The pre-pro-protein is processed into the mature growth factor domain (GFD) bound to the prodomain upon secretion61. b Plot of GDF2 mutations found only in PAH cases superimposed on the structure of prodomain bound GDF2 (PDB: 4YCG)21. The GDF2 growth factor domain is shown in green and the prodomain in cyan. c Magnified view of the Arg110 and Glu143 mutations. The wild-type amino acids make double salt bridges to stabilise the prodomain conformation at the interface between the growth factor domain and prodomain. The E143K and R110W mutations both disrupt these interactions, destabilising the interaction between the growth factor domain and prodomain. d GDF2 levels secreted into supernatants of HEK293T cells transfected with likely pathogenic variants found in PAH cases, compared with wild-type GDF2 and cells transfected with an empty vector. ***P < 0.001 by ANOVA

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