Figure 7:

Model for inhibition of Vt-induced F-actin bundle by wild-type MVt (labeled as MVt(WT)) but failure of that by MVt cardiomyopathy mutants (labeled as MVt(CM)). (A) Release of H1 upon F-actin engagement enables Vt dimerization thus resulting in parallel F-actin bundle formation. (B) An additional protruding structural sub-domain formed by the insert and displaced H1 at the N-terminus of MVt(WT) blocks homo- or hetero-dimer formation with Vt, thus preventing F-actin bundling. (C) The protruding sub-domain is destabilized by the cardiomyopathy related mutations in MVt(CM), resulting in disordered F-actin assemblies due to alternative interactions with another subunit of MVt(CM) (left) or a subunit of Vt (right).