4LG4

Structural Basis for Autoactivation of Human Mst2 Kinase and Its Regulation by RASSF5

4LG4 の概要

• エントリーDOI: 10.2210/pdb4lg4/pdb
• 関連するPDBエントリー: 4LGD
• 分子名称: Serine/threonine-protein kinase 3, GLYCEROL (3 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)
• 細胞内の位置: Cytoplasm : Q13188
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 204200.45

構造登録者

Luo, X.,Ni, L.,Tomchick, D.R. (登録日: 2013-06-27, 公開日: 2013-09-18, 最終更新日: 2023-09-20)

主引用文献

Ni, L.,Li, S.,Yu, J.,Min, J.,Brautigam, C.A.,Tomchick, D.R.,Pan, D.,Luo, X.
Structural Basis for Autoactivation of Human Mst2 Kinase and Its Regulation by RASSF5.
Structure, 21:1757-1768, 2013

PubMed Abstract: The tumor-suppressive Hippo pathway controls tissue homeostasis through balancing cell proliferation and apoptosis. Activation of the kinases Mst1 and Mst2 (Mst1/2) is a key upstream event in this pathway and remains poorly understood. Mst1/2 and their critical regulators RASSFs contain Salvador/RASSF1A/Hippo (SARAH) domains that can homo- and heterodimerize. Here, we report the crystal structures of human Mst2 alone and bound to RASSF5. Mst2 undergoes activation through transautophosphorylation at its activation loop, which requires SARAH-mediated homodimerization. RASSF5 disrupts Mst2 homodimer and blocks Mst2 autoactivation. Binding of RASSF5 to already activated Mst2, however, does not inhibit its kinase activity. Thus, RASSF5 can act as an inhibitor or a potential positive regulator of Mst2, depending on whether it binds to Mst2 before or after activation-loop phosphorylation. We propose that these temporally sensitive functions of RASSFs enable the Hippo pathway to respond to and integrate diverse cellular signals.

PubMed: 23972470
DOI: 10.1016/j.str.2013.07.008

実験手法

X-RAY DIFFRACTION (2.42 Å)