Biophysical characterization of naturally occurring titin M10 mutations.

ABSTRACT: The giant proteins titin and obscurin are important for sarcomeric organization, stretch response, and sarcomerogenesis in myofibrils. The extreme C-terminus of titin (the M10 domain) binds to the N-terminus of obscurin (the Ig1 domain) in the M-band. The high-resolution structure of human M10 has been solved, along with M10 bound to one of its two known molecular targets, the Ig1 domain of obscurin-like. Multiple M10 mutations are linked to limb-girdle muscular dystrophy type 2J (LGMD2J) and tibial muscular dystrophy (TMD). The effect of the M10 mutations on protein structure and function has not been thoroughly characterized. We have engineered all four of the naturally occurring human M10 missense mutants and biophysically characterized them in vitro. Two of the four mutated constructs

SUBMITTER: Rudloff MW 

PROVIDER: S-EPMC4456108 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature