Telethonin [SEP] found in taxon
-related diseases.
Two mutations in Telethonin, Thr137Ile and Arg153His have been associated with hypertrophic cardiomyopathy, which enhance the binding of Telethonin with Titin and MYOZ2. The Glu132Gln mutation has been associated with dilated cardiomyopathy, which has the opposite effect in that it impairs the binding of Telethonin with Titin and MYOZ2. Mutations in Titin associated with dilated cardiomyopathy, including Val54Met, have been shown specifically to impair binding of Titin with Telethonin. In a mouse model of dilated cardiomyopathy, recapitulating the human dilated cardiomyopathy mutation in MLP, Trp4Arg
which enables antiparallel association with the Titin Z1-Z2 domains in cardiac and skeletal muscle. Structural analysis of full-length Telethonin with the N-terminal region of Titin indicate that the C-terminus of Telethonin is critical for the dimerization of two Telethonin/Titin complexes into a higher oligomeric structure.
Function.
Telethonin expression is developmentally regulated in both cardiac and skeletal muscle and is thought to be critical to sarcomere assembly. Telethonin was found to be a late assembling protein only present in mature myofibrils at Z-discs.