3ZHP

Human MST3 (STK24) in complex with MO25beta

3ZHP の概要

• エントリーDOI: 10.2210/pdb3zhp/pdb
• 分子名称: CALCIUM-BINDING PROTEIN 39-LIKE, SERINE/THREONINE-PROTEIN KINASE 24, SULFATE ION (3 entities in total)
• 機能のキーワード: cell cycle, mo25
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm: Q9Y6E0
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 145549.47

構造登録者

Elkins, J.M.,Szklarz, M.,Krojer, T.,Mehellou, Y.,Alessi, D.R.,Chaikaud, A.,von Delft, F.,Bountra, C.,Edwards, A.,Knapp, S. (登録日: 2012-12-24, 公開日: 2013-01-16, 最終更新日: 2023-12-20)

主引用文献

Mehellou, Y.,Alessi, D.R.,Macartney, T.J.,Szklarz, M.,Knapp, S.,Elkins, J.M.
Structural Insights Into the Activation of Mst3 by Mo25.
Biochem.Biophys.Res.Commun., 431:604-, 2013

PubMed Abstract: The MO25 scaffolding protein operates as critical regulator of a number of STE20 family protein kinases (e.g. MST and SPAK isoforms) as well as pseudokinases (e.g. STRAD isoforms that play a critical role in activating the LKB1 tumour suppressor). To better understand how MO25 interacts and stimulates the activity of STE20 protein kinases, we determined the crystal structure of MST3 catalytic domain (residues 19-289) in complex with full length MO25β. The structure reveals an intricate web of interactions between MST3 and MO25β that function to stabilise the kinase domain in a closed, active, conformation even in the absence of ATP or an ATP-mimetic inhibitor. The binding mode of MO25β is reminiscent of the mechanism by which MO25α interacts with the pseudokinase STRADα. In particular we identified interface residues Tyr223 of MO25β and Glu58 and Ile71 of MST3 that when mutated prevent activation of MST3 by MO25β. These data provide molecular understanding of the mechanism by which MO25 isoforms regulates the activity of STE20 family protein kinases.

PubMed: 23296203
DOI: 10.1016/J.BBRC.2012.12.113

実験手法

X-RAY DIFFRACTION (2.9 Å)