2WTK

Structure of the heterotrimeric LKB1-STRADalpha-MO25alpha complex

2WTK の概要

• エントリーDOI: 10.2210/pdb2wtk/pdb
• 関連するPDBエントリー: 1UPK 1UPL
• 分子名称: CALCIUM-BINDING PROTEIN 39, STE20-RELATED KINASE ADAPTER PROTEIN ALPHA, SERINE/THREONINE-PROTEIN KINASE 11, ... (6 entities in total)
• 機能のキーワード: transferase-metal-binding protein complex, transferase metal-binding protein complex, kinase, nucleus, serine/threonine-protein kinase, pseudokinase, phosphoprotein, signal transduction, transferase, nucleotide-binding, transferase/metal-binding protein
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm (Potential): Q9Y376; Nucleus: Q7RTN6 Q15831
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 234063.08

構造登録者

Zeqiraj, E.,van Aalten, D.M.F. (登録日: 2009-09-16, 公開日: 2009-12-15, 最終更新日: 2023-12-20)

主引用文献

Zeqiraj, E.,Filippi, B.M.,Deak, M.,Alessi, D.R.,Van Aalten, D.M.F.
Structure of the Lkb1-Strad-Mo25 Complex Reveals an Allosteric Mechanism of Kinase Activation.
Science, 326:1707-, 2009

PubMed Abstract: The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK). LKB1 activity is regulated by the pseudokinase STRADalpha and the scaffolding protein MO25alpha through an unknown, phosphorylation-independent, mechanism. We describe the structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation. STRADalpha adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRADalpha and MO25alpha promote the active conformation of LKB1, which is stabilized by MO25alpha interacting with the LKB1 activation loop. This previously undescribed mechanism of kinase activation may be relevant to understanding the evolution of other pseudokinases. The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function.

PubMed: 19892943
DOI: 10.1126/SCIENCE.1178377

実験手法

X-RAY DIFFRACTION (2.65 Å)