Giant protein kinases: domain interactions and structural basis of autoregulation.

摘要: The myosin-associated giant protein kinases twitchin and titin are composed predominantly of fibronectin- immunoglobulin-like modules, We report the crystal structures two autoinhibited kinase fragments, one from Aplysia a larger fragment Caenorhabditis elegans containing an additional C-terminal domain, structure longer shoes that immunoglobulin domain contacts on opposite side catalytic cleft, laterally exposing potential myosin binding residues, Together, reveal cooperative interactions between autoregulatory region residues involved in substrate binding, ATP catalysis activation loop, explain differences observed autoinhibitory mechanism found calmodulin-dependent I.