6AO5

Crystal structure of human MST2 in complex with SAV1 SARAH domain

6AO5 の概要

• エントリーDOI: 10.2210/pdb6ao5/pdb
• 分子名称: Serine/threonine-protein kinase 3, Protein salvador homolog 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• 機能のキーワード: hippo, mst autoactivation, dimerization, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q13188; Nucleus : Q9H4B6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53535.43

構造登録者

Tomchick, D.R.,Luo, X.,Ni, L. (登録日: 2017-08-15, 公開日: 2017-11-08, 最終更新日: 2023-10-04)

主引用文献

Bae, S.J.,Ni, L.,Osinski, A.,Tomchick, D.R.,Brautigam, C.A.,Luo, X.
SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK.
Elife, 6:-, 2017

PubMed Abstract: The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAK as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1-MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAK PP2A phosphatase complex.

PubMed: 29063833
DOI: 10.7554/eLife.30278

実験手法

X-RAY DIFFRACTION (2.955 Å)