To help maintain the highly ordered sarcomeric structure of myofibrils, the myosin-containing contractile filaments of striated muscle are crosslinked with other proteins at the M-band region of the sarcomere. The proteins titin and myomesin are known to interact with myosin filaments at the M-band, but the role of other M-band-localised proteins – such as the giant protein obscurin – is less well understood. On , Mathias Gautel and colleagues explore the interprotein interactions of obscurin and its newly discovered homologue obscurin-like 1 (Obsl1). Using a yeast two-hybrid system, the authors show that obscurin and Obsl1 both interact with myomesin and with the extreme C-terminal M10 domain of titin; moreover, obscurin can form a ternary complex with titin and myomesin. The M-band localisation of obscurin is disrupted when the titin- or myomesin-binding domains of obscurin (or the corresponding domains of myomesin and titin) are overexpressed, or when myomesin is knocked down. Importantly, muscle-disease-associated mutations in the titin M10 domain weaken the interaction between titin and obscurin or Obsl1. Based on their data, the authors propose a revised model of protein interactions at the M-band.
