Structural basis for activation of the titin kinase domain during myofibrillogenesis

摘要: The giant muscle protein titin (connectin) is essential in the temporal and spatial control of assembly highly ordered sarcomeres (contractile units) striated muscle. Here we present crystal structure titin's only catalytic domain, an autoregulated serine kinase (titin kinase). shows how active site inhibited by a tyrosine domain. We describe dual mechanism activation that consists phosphorylation this binding calcium/calmodulin to regulatory tail. domain first known non-arginine–aspartate be activated phosphorylation. phosphorylated not located segment, as other kinases, but P+ 1 loop, indicating partner titinkinase substrate. Titin phosphorylates telethonin early differentiating myocytes, may act myofibrillogenesis.