S.flexneri ipaH9.8 binds GBPs

Stable Identifier
R-HSA-9955144
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Shigella flexneri
Compartment
cytosol
ReviewStatus
5/5
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S.flexneri ipaH9.8 binds GBPs
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The Gram-negative intracellular bacterium Shigella flexneri secretes the effector protein ipaH9.8 into host cells through its type III secretion system. Within host cells, IpaH9.8 functions as an E3 ubiquitin ligase, recruiting host E2 ubiquitin-conjugating enzymes and catalyzing the attachment of K48-linked polyubiquitin chains to target proteins (Rohde JR et al., 2007; Edwards DJ et al., 2014; Keszei AFA & Sicheri F 2017). Among the substrates of IpaH9.8 are guanylate-binding proteins (GBPs), including GBP1, GBP2, GBP4, and GBP6. The K48-linked polyubiquitin chains mark GBPs for recognition and degradation by the 26S proteasome, thereby abrogating their antimicrobial functions. GBP3 and GBP7 are not targeted by ipaH9.8 for ubiquitination (Wandel MP et al., 2017; Li P et al., 2017; Ji C et al. 2019; Ye Y et al., 2020; Goers L et al., 2023).
Literature References
PubMed ID Title Journal Year
29144452 Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defence

Li, P, Jiang, W, Yu, Q, Liu, W, Zhou, P, Li, J, Xu, J, Xu, B, Wang, F, Shao, F

Nature 2017
31216343 Structural mechanism for guanylate-binding proteins (GBPs) targeting by the Shigella E3 ligase IpaH9.8

Ji, C, Du, S, Li, P, Zhu, Q, Yang, X, Long, C, Yu, J, Shao, F, Xiao, J

PLoS Pathog 2019
29024643 GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8

Wandel, MP, Pathe, C, Werner, EI, Ellison, CJ, Boyle, KB, von der Malsburg, A, Rohde, J, Randow, F

Cell Host Microbe 2017
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Cross References
Mondo
Authored
Shamovsky, V  (2025-06-10)
Reviewed
Daumke, O  (2025-10-31)
Created
Shamovsky, V  (2025-06-10)
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