Introduction
Recently, the Pingshan Biomedical R&D and Transformation Center of Shenzhen Bay Laboratory collaborated with the Shenzhen Graduate School of Peking University to publish a research paper titled "Substrate-binding stabilizes the hydrodynamic cluster to understand the inhibition of bacterial ubiquitin ligase IpaH9.8" in the sub journal "Communications Biology" of Nature, This article introduces the new progress made in the study of the activation mechanism of bacterial E3 enzymes. This study focuses on the Shigella E3 enzyme IpaH9.8, and elucidates the mechanism of IpaH9.8 self inhibition and substrate induced activation by analyzing the crystal structure of the full length protein of IpaH9.8 and its complex with substrate protein hGBP1.
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Recently, the Pingshan Biomedical R&D and Transformation Center of Shenzhen Bay Laboratory collaborated with the Shenzhen Graduate School of Peking University to publish a research paper titled "Substrate-binding stabilizes the hydrodynamic cluster to understand the inhibition of bacterial ubiquitin ligase IpaH9.8" in the sub journal "Communications Biology" of Nature, This article introduces the new progress made in the study of the activation mechanism of bacterial E3 enzymes. This study focuses on the Shigella E3 enzyme IpaH9.8, and elucidates the mechanism of IpaH9.8 self inhibition and substrate induced activation by analyzing the crystal structure of the full length protein of IpaH9.8 and its complex with substrate protein hGBP1.
IpaH family proteins are E3 Ubiquitin ligase from Gram-negative bacteria, which are composed of three parts: the N-terminal T3SS signal sequence, the LRR domain responsible for binding the substrate, and the C-terminal conserved NEL domain with E3 enzyme function. These E3 enzymes can inhibit host inflammation and endogenous immune response by hijacking the host's ubiquitin Proteasome signaling pathway, thus promoting the infection process. In host cells, in order to avoid self ubiquitination and degradation by the host's ubiquitin system, or to avoid the production of free Ub chains that activate the host immune response, IpaH proteins are usually in a self inhibitory state when there is no substrate. IpaH9.8 is an E3 enzyme secreted by Shigella, which can target ubiquitination to degrade NEMO (NF) in host cells- κ B regulator), GBP1 (Guanylate-binding protein 1) and other proteins, which in turn affect the immune response of the host. In this study,
