Kobe B, Heierhorst J, Feil S C, Parker M W, Benian G M, Weiss K R, Kemp B E
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
EMBO J. 1996 Dec 16;15(24):6810-21.
The myosin-associated giant protein kinases twitchin and titin are composed predominantly of fibronectin- and immunoglobulin-like modules. We report the crystal structures of two autoinhibited twitchin kinase fragments, one from Aplysia and a larger fragment from Caenorhabditis elegans containing an additional C-terminal immunoglobulin-like domain. The structure of the longer fragment shows that the immunoglobulin domain contacts the protein kinase domain on the opposite side from the catalytic cleft, laterally exposing potential myosin binding residues. Together, the structures reveal the cooperative interactions between the autoregulatory region and the residues from the catalytic domain involved in protein substrate binding, ATP binding, catalysis and the activation loop, and explain the differences between the observed autoinhibitory mechanism and the one found in the structure of calmodulin-dependent kinase I.
与肌球蛋白相关的巨蛋白激酶抽动蛋白和肌联蛋白主要由纤连蛋白和免疫球蛋白样模块组成。我们报道了两个自身抑制的抽动蛋白激酶片段的晶体结构，一个来自海兔，另一个来自秀丽隐杆线虫的更大片段，该片段包含一个额外的C端免疫球蛋白样结构域。较长片段的结构表明，免疫球蛋白结构域在与催化裂隙相对的一侧与蛋白激酶结构域接触，侧向暴露潜在的肌球蛋白结合残基。这些结构共同揭示了自身调节区域与催化结构域中参与蛋白底物结合、ATP结合、催化和激活环的残基之间的协同相互作用，并解释了观察到的自身抑制机制与钙调蛋白依赖性激酶I结构中发现的机制之间的差异。
