Here, we demonstrate that the metavinculin-specific helix H1' plays an important role for protein stability of the tail domain, since a point mutation in this helix, R975W, which is associated with the occurrence of dilated cardiomyopathy in man, further decreases thermal stability of the metavinculin tail domain.
The R975W mutation, in the alternatively spliced exon 19 of vinculin (VCL) which yields the isoform metavinculin, was associated previously with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and shown to alter in vivo organization of intercalated discs.