An allosteric regulation mechanism of Arabidopsis Serine/Threonine kinase 1 (SIK1) through phosphorylation.
An allosteric regulation mechanism of Arabidopsis Serine/Threonine kinase 1 (SIK1) through phosphorylation.
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拟南芥丝氨酸/苏氨酸激酶 1 (SIK1) 通过磷酸化的变构调节机制
DOI：
10.1016/j.csbj.2021.12.033
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发表时间：
2022
影响因子：
6
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Mu J;Zhou J;Gong Q;Xu Q
拟南芥丝氨酸/苏氨酸激酶1（SIK1）是一种不育20（STE20）/河马直向同源物，也被归类为促分裂原活化蛋白激酶（MAP4K）。与其动物和真菌直系同源物一样，SIK1是细胞周期退出、细胞扩增、极性建立以及致病反应所必需的。与其他MAPK一样，SIK1的催化活性可能受其磷酸化状态的调节。由于没有晶体结构的SIK1尚未报道，我们建立了结构模型的SIK1激酶结构域在不同的磷酸化状态与不同的口袋构象，看看这种激酶可能受到调控。使用计算结构生物学方法，我们概述了一个传导路径，其中A环上的磷酸化位点通过控制G环催化口袋的关闭或打开来调节SIK1的催化活性。此外，通过对动态运动和体外激酶测定的分析，我们证实了该传导路径中的三个关键残基，Lys278，Glu295和Arg370，确实对SIK1的激酶活性很重要。由于这些残基在所有检测的STE20激酶中是保守的，因此我们发现的调节机制可能在STE20激酶中是共同的。
The Arabidopsis Serine/Threonine Kinase 1 (SIK1) is a Sterile 20 (STE20)/Hippo orthologue that is also categorized as a Mitogen-Activated Protein Kinase Kinase Kinase Kinase (MAP4K). Like its animal and fungi orthologues, SIK1 is required for cell cycle exit, cell expansion, polarity establishment, as well as pathogenic response. The catalytic activity of SIK1, like other MAPKs, is presumably regulated by its phosphorylation states. Since no crystal structure for SIK1 has been reported yet, we built structural models for SIK1 kinase domain in different phosphorylation states with different pocket conformation to see how this kinase may be regulated. Using computational structural biology methods, we outlined a conduction path in which a phosphorylation site on the A-loop regulates the catalytic activity of SIK1 by controlling the closing or opening of the catalytic pocket at the G-loop. Furthermore, with analyses on the dynamic motions and in vitro kinase assay, we confirmed that three key residues in this conduction path, Lys278, Glu295, and Arg370, are indeed important for the kinase activity of SIK1. Since these residues are conserved in all STE20 kinases examined, the regulatory mechanism that we discovered may be common in STE20 kinases.
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影响因子：
5.5
作者：
Goetz, Andreas W.;Williamson, Mark J.;Xu, Dong;Poole, Duncan;Le Grand, Scott;Walker, Ross C.
通讯作者：
Walker, Ross C.
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
影响因子：
5.7
作者：
Eswaran, Jeyanthy;Lee, Wen Hwa;Debreczeni, Judit E.;Filippakopoulos, Panagis;Turnbull, Andrew;Fedorov, Oleg;Deacon, Sean W.;Peterson, Jeffrey R.;Knapp, Stefan
通讯作者：
Knapp, Stefan
DOI：
10.1107/s0907444909047507
发表时间：
2010-02-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Ko, Tzu-Ping;Jeng, Wen-Yih;Wang, Andrew H. -J.
通讯作者：
Wang, Andrew H. -J.
DOI：
10.1002/prot.340110305
发表时间：
1991-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
ICHIYE, T;KARPLUS, M
通讯作者：
KARPLUS, M