7K36

Cryo-EM structure of STRIPAK complex

7K36 の概要

• エントリーDOI: 10.2210/pdb7k36/pdb
• EMDBエントリー: 22650
• 分子名称: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Striatin-3, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, ... (8 entities in total)
• 機能のキーワード: phosphorylation, complex, pp2a, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 612842.75

構造登録者

Jeong, B.-C.,Bai, X.C. (登録日: 2020-09-10, 公開日: 2021-03-10, 最終更新日: 2024-03-06)

主引用文献

Jeong, B.C.,Bae, S.J.,Ni, L.,Zhang, X.,Bai, X.C.,Luo, X.
Cryo-EM structure of the Hippo signaling integrator human STRIPAK.
Nat.Struct.Mol.Biol., 28:290-299, 2021

PubMed Abstract: The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse cellular signals in the Hippo pathway to regulate cell proliferation and survival. The architecture and assembly mechanism of this critical complex are poorly understood. Using cryo-EM, we determine the structure of the human STRIPAK core comprising PP2AA, PP2AC, STRN3, STRIP1, and MOB4 at 3.2-Å resolution. Unlike the canonical trimeric PP2A holoenzyme, STRIPAK contains four copies of STRN3 and one copy of each the PP2AA-C heterodimer, STRIP1, and MOB4. The STRN3 coiled-coil domains form an elongated homotetrameric scaffold that links the complex together. An inositol hexakisphosphate (IP) is identified as a structural cofactor of STRIP1. Mutations of key residues at subunit interfaces disrupt the integrity of STRIPAK, causing aberrant Hippo pathway activation. Thus, STRIPAK is established as a noncanonical PP2A complex with four copies of regulatory STRN3 for enhanced signal integration.

PubMed: 33633399
DOI: 10.1038/s41594-021-00564-y

実験手法

ELECTRON MICROSCOPY (3.3 Å)