6LOL

The crystal structure of full length IpaH9.8

Summary for 6LOL

• Entry DOI: 10.2210/pdb6lol/pdb
• Descriptor: E3 ubiquitin-protein ligase ipaH9.8 (1 entity in total)
• Functional Keywords: e3, ipah9.8, transferase
• Biological source: Shigella flexneri 2002017
• Total number of polymer chains: 1
• Total formula weight: 59922.64

Authors

Ye, Y.,Huang, H. (deposition date: 2020-01-06, release date: 2020-12-23, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.75 Å)