6MCQ

L. pneumophila effector kinase LegK7 in complex with human MOB1A

6MCQ の概要

• エントリーDOI: 10.2210/pdb6mcq/pdb
• 関連するPDBエントリー: 6MCP
• 分子名称: LegK7, MOB kinase activator 1A, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• 機能のキーワード: translocated effector, ser/thr protein kinase, allosteric activation, hippo pathway, transferase
• 由来する生物種: Legionella pneumophila subsp. pneumophila; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 168354.70

構造登録者

Beyrakhova, K.A.,Xu, C.,Boniecki, M.T.,Cygler, M. (登録日: 2018-09-01, 公開日: 2019-09-04, 最終更新日: 2024-03-13)

主引用文献

Lee, P.C.,Beyrakhova, K.,Xu, C.,Boniecki, M.T.,Lee, M.H.,Onu, C.J.,Grishin, A.M.,Machner, M.P.,Cygler, M.
TheLegionellakinase LegK7 exploits the Hippo pathway scaffold protein MOB1A for allostery and substrate phosphorylation.
Proc.Natl.Acad.Sci.USA, 117:14433-14443, 2020

PubMed Abstract: During infection, the bacterial pathogen manipulates a variety of host cell signaling pathways, including the Hippo pathway which controls cell proliferation and differentiation in eukaryotes. Our previous studies revealed that encodes the effector kinase LegK7 which phosphorylates MOB1A, a highly conserved scaffold protein of the Hippo pathway. Here, we show that MOB1A, in addition to being a substrate of LegK7, also functions as an allosteric activator of its kinase activity. A crystallographic analysis of the LegK7-MOB1A complex revealed that the N-terminal half of LegK7 is structurally similar to eukaryotic protein kinases, and that MOB1A directly binds to the LegK7 kinase domain. Substitution of interface residues critical for complex formation abrogated allosteric activation of LegK7 both in vitro and within cells and diminished MOB1A phosphorylation. Importantly, the N-terminal extension (NTE) of MOB1A not only regulated complex formation with LegK7 but also served as a docking site for downstream substrates such as the transcriptional coregulator YAP1. Deletion of the NTE from MOB1A or addition of NTE peptides as binding competitors attenuated YAP1 recruitment to and phosphorylation by LegK7. By providing mechanistic insight into the formation and regulation of the LegK7-MOB1A complex, our study unravels a sophisticated molecular mimicry strategy that is used by to take control of the host cell Hippo pathway.

PubMed: 32513747
DOI: 10.1073/pnas.2000497117

実験手法

X-RAY DIFFRACTION (2.57 Å)