4LQS

Crystal structure of the Cbk1-Mob2 kinase-coactivator complex

4LQS の概要

• エントリーDOI: 10.2210/pdb4lqs/pdb
• 関連するPDBエントリー: 4LQP 4LQQ
• 分子名称: Serine/threonine-protein kinase CBK1, CBK1 kinase activator protein MOB2, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: kinase, transferase-transferase activator complex, transferase/transferase activator
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• 細胞内の位置: Nucleus: P43563
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87677.96

構造登録者

Gogl, G.,Remenyi, A. (登録日: 2013-07-19, 公開日: 2014-07-30, 最終更新日: 2024-02-28)

主引用文献

Gogl, G.,Schneider, K.D.,Yeh, B.J.,Alam, N.,Nguyen Ba, A.N.,Moses, A.M.,Hetenyi, C.,Remenyi, A.,Weiss, E.L.
The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase-Coactivator System and Substrate Docking Mechanism.
Plos Biol., 13:e1002146-e1002146, 2015

PubMed Abstract: Eukaryotic cells commonly use protein kinases in signaling systems that relay information and control a wide range of processes. These enzymes have a fundamentally similar structure, but achieve functional diversity through variable regions that determine how the catalytic core is activated and recruited to phosphorylation targets. "Hippo" pathways are ancient protein kinase signaling systems that control cell proliferation and morphogenesis; the NDR/LATS family protein kinases, which associate with "Mob" coactivator proteins, are central but incompletely understood components of these pathways. Here we describe the crystal structure of budding yeast Cbk1-Mob2, to our knowledge the first of an NDR/LATS kinase-Mob complex. It shows a novel coactivator-organized activation region that may be unique to NDR/LATS kinases, in which a key regulatory motif apparently shifts from an inactive binding mode to an active one upon phosphorylation. We also provide a structural basis for a substrate docking mechanism previously unknown in AGC family kinases, and show that docking interaction provides robustness to Cbk1's regulation of its two known in vivo substrates. Co-evolution of docking motifs and phosphorylation consensus sites strongly indicates that a protein is an in vivo regulatory target of this hippo pathway, and predicts a new group of high-confidence Cbk1 substrates that function at sites of cytokinesis and cell growth. Moreover, docking peptides arise in unstructured regions of proteins that are probably already kinase substrates, suggesting a broad sequential model for adaptive acquisition of kinase docking in rapidly evolving intrinsically disordered polypeptides.

PubMed: 25966461
DOI: 10.1371/journal.pbio.1002146

実験手法

X-RAY DIFFRACTION (3.3 Å)