Fig. 1: Cardiomyopathy related iASPP mutants are aggregation prone.
From: Cardiocutaneous syndrome is caused by aggregation of iASPP mutants
A Schematic illustration of the structure of iASPP and localization of published cardiomyopathy associated mutations. Alternative C-termini resulting from frameshift mutations are shown in orange. B Crystal structure of the iASPP CTD (PDB: 2VGE) with highlighted missense mutations represented in stick mode. C Aggregation propensity prediction for the iASPP CTD using TANGO analysis. The frameshift mutation 2486_2487delinsTC leads to a 5’UTR extension predicted to be highly aggregation prone. D Blue Native PAGE (upper) and SDS PAGE (lower) of Myc-tagged iASPP WT and the indicated mutants. Proteins were expressed in transiently transfected H1299 cells and Western Blots were analyzed using an anti-Myc antibody. SDS PAGE was visualised using light and dark exposure (exp.). The F815A mutant is an artificial mutant used as a control mutant with a destabilized hydrophobic core. E Insoluble fractions of Myc-tagged iASPP WT or mutants. Proteins were expressed in transiently transfected H1299 cells and solubility was analysed via Western Blot. (Mean ± SD. n = 3, ordinary one-way ANOVA, n.s. P > 0.05; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001).
