6LOJ

The complex structure of IpaH9.8-LRR and hGBP1

6LOJ の概要

• エントリーDOI: 10.2210/pdb6loj/pdb
• 分子名称: Invasion plasmid antigen, Guanylate-binding protein 1, GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: ipah9.8, hgbp1, lrr, transferase, ligase-hydrolase complex, ligase/hydrolase
• 由来する生物種: Shigella flexneri; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94438.98

構造登録者

Ye, Y.,Huang, H. (登録日: 2020-01-06, 公開日: 2020-12-23, 最終更新日: 2023-11-29)

主引用文献

Ye, Y.,Xiong, Y.,Huang, H.
Substrate-binding destabilizes the hydrophobic cluster to relieve the autoinhibition of bacterial ubiquitin ligase IpaH9.8.
Commun Biol, 3:752-752, 2020

PubMed Abstract: IpaH enzymes are bacterial E3 ligases targeting host proteins for ubiquitylation. Two autoinhibition modes of IpaH enzymes have been proposed based on the relative positioning of the Leucine-rich repeat domain (LRR) with respect to the NEL domain. In mode 1, substrate-binding competitively displaces the interactions between theLRR and NEL to relieve autoinhibition. However, the molecular basis for mode 2 is unclear. Here, we present the crystal structures of Shigella IpaH9.8 and the LRR of IpaH9.8 in complex with the substrate of human guanylate-binding protein 1 (hGBP1). A hydrophobic cluster in the C-terminus of IpaH9.8 forms a hydrophobic pocket involved in binding the NEL domain, and the binding is important for IpaH9.8 autoinhibition. Substrate-binding destabilizes the hydrophobic cluster by inducing conformational changes of IpaH9.8. Arg166 and Phe187 in IpaH9.8 function as sensors for substrate-binding. Collectively, our findings provide insights into the molecular mechanisms for the actication of IpaH9.8 in autoinhibition mode 2.

PubMed: 33303953
DOI: 10.1038/s42003-020-01492-1

実験手法

X-RAY DIFFRACTION (3.72 Å)