PK1 from Drosophila obscurin is an inactive pseudokinase with scaffolding properties.
PK1 from Drosophila obscurin is an inactive pseudokinase with scaffolding properties.
复制标题
作者：
Obscurins是一种大型丝状蛋白质，在肌肉的组装、稳定和调节中起着关键作用。这些蛋白质的特征是两个C-末端激酶结构域PK 1和PK 2的串联，它们被长的内在无序序列分开。这种保守结构域排列的意义尚不清楚。我们的研究PK 1从果蝇obscurin表明，这是一个假激酶的CAM激酶家族的典型特征，但它携带一个最小的监管尾巴，不再结合钙调蛋白或具有典型的其他肌节激酶mechanosensory性能。PK 1以高亲和力结合ATP，但不存在镁并且缺乏可检测的磷酸转移活性。它也有一个高度分散的活性位点，在节肢动物中严格保守，可能已经进化到适应非传统的粘合剂。我们发现，PK 1与PK 2相互作用，这表明后者的功能关系。这些发现使我们推测PK 1/PK 2形成假激酶/激酶双系统，其中PK 1可能充当PK 2的变构调节剂，并且其中机械感测特性类似于肌联蛋白样激酶中的调节尾，现在可能位于非结构化的激酶间片段上。我们建议，PK 1-interkinase-PK 2区域构成了一个集成的功能单位在obscurin蛋白。
Obscurins are large filamentous proteins with crucial roles in the assembly, stability and regulation of muscle. Characteristic of these proteins is a tandem of two C-terminal kinase domains, PK1 and PK2, that are separated by a long intrinsically disordered sequence. The significance of this conserved domain arrangement is unknown. Our study of PK1 from Drosophila obscurin shows that this is a pseudokinase with features typical of the CAM-kinase family, but which carries a minimalistic regulatory tail that no longer binds calmodulin or has mechanosensory properties typical of other sarcomeric kinases. PK1 binds ATP with high affinity, but in the absence of magnesium and lacks detectable phosphotransfer activity. It also has a highly diverged active site, strictly conserved across arthropods, that might have evolved to accommodate an unconventional binder. We find that PK1 interacts with PK2, suggesting a functional relation to the latter. These findings lead us to speculate that PK1/PK2 form a pseudokinase/kinase dual system, where PK1 might act as an allosteric regulator of PK2 and where mechanosensing properties, akin to those described for regulatory tails in titin-like kinases, might now reside on the unstructured interkinase segment. We propose that the PK1-interkinase-PK2 region constitutes an integrated functional unit in obscurin proteins.
登录
查看更多内容
DOI：
10.1083/jcb.132.5.835
发表时间：
1996-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Benian GM;Tinley TL;Tang X;Borodovsky M
通讯作者：
Borodovsky M
DOI：
10.1042/bj20141441
发表时间：
2015-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Bailey FP;Byrne DP;Oruganty K;Eyers CE;Novotny CJ;Shokat KM;Kannan N;Eyers PA
通讯作者：
Eyers PA
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1016/j.bbcan.2021.188567
发表时间：
2021-08
期刊：
Biochimica et biophysica acta. Reviews on cancer
影响因子：
--
作者：
Guardia T;Eason M;Kontrogianni-Konstantopoulos A
通讯作者：
Kontrogianni-Konstantopoulos A
DOI：
10.1016/bs.mie.2022.03.028
发表时间：
2022-01-01
期刊：
PSEUDOKINASES
影响因子：
--
作者：
Bogomolovas, Julius;Gravenhorst, Peter;Mayans, Olga
通讯作者：
Mayans, Olga