Striated muscle architecture is complex by necessity; the myocyte must balance contrasting needs of structural integrity and motion.  The giant muscle protein obscurin assists myofibrils in this task through sarcomere organization, stretch signaling, and linking of the muscle contractile apparatus with the sarcoplasmic reticulum (SR).  Here, we present the preliminary structure of the extreme N-terminus of this molecule. NMR data indicate this region folds as an Ig-like motif, with one face showing a large number of solvent-exposed hydrophobic residues.  Chemical shift analysis to a known binding partner, the M10 domain of titin, suggests a protein-protein binding event primarily at this hydrophobic face of the obscurin domain.  Binding specificity is likely achieved through several charged residues near the hydrophobic patch.  Mutations of the M10 domain are associated with limb-girdle muscular dystrophy, and thus fully understanding this obscurin-titin interaction may help elucidate the biochemical mechanism behind this disease.

Solution structure and function of the Ig1 domain of the giant muscle protein Obscurin

244th National Meeting (2012)

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