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An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins

Apte, S and Bhutda, S and Ghosh, S and Sharma, K and Barton, TE and Dibyachintan, S and Sahay, O and Roy, S and Sinha, AR and Adicherla, H and Rakshit, J and Tang, S and Datey, A and Santra, S and Joseph, J and Sasidharan, S and Hammerschmidt, S and Chakravortty, D and Oggioni, MR and Santra, MK and Neill, DR and Banerjee, A (2023) An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins. In: Science advances, 9 (12). eade1851.

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Official URL: https://doi.org/10.1126/sciadv.ade1851


Sensing of pathogens by ubiquitination is a critical arm of cellular immunity. However, universal ubiquitination targets on microbes remain unidentified. Here, using in vitro, ex vivo, and in vivo studies, we identify the first protein-based ubiquitination substrates on phylogenetically diverse bacteria by unveiling a strategy that uses recognition of degron-like motifs. Such motifs form a new class of intra-cytosolic pathogen-associated molecular patterns (PAMPs). Their incorporation enabled recognition of nonubiquitin targets by host ubiquitin ligases. We find that SCFFBW7 E3 ligase, supported by the regulatory kinase, glycogen synthase kinase 3β, is crucial for effective pathogen detection and clearance. This provides a mechanistic explanation for enhanced risk of infections in patients with chronic lymphocytic leukemia bearing mutations in F-box and WD repeat domain containing 7 protein. We conclude that exploitation of this generic pathogen sensing strategy allows conservation of host resources and boosts antimicrobial immunity.

Item Type: Journal Article
Publication: Science advances
Publisher: NLM (Medline)
Additional Information: The copyright for this article belongs to the Authors.
Keywords: bacterial protein; cell cycle protein; F box protein; F box/WD repeat containing protein 7; membrane protein, bacterium; genetics; human; metabolism; phosphorylation; ubiquitination, Bacteria; Bacterial Proteins; Cell Cycle Proteins; F-Box Proteins; F-Box-WD Repeat-Containing Protein 7; Humans; Membrane Proteins; Phosphorylation; Ubiquitination
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 21 Apr 2023 09:43
Last Modified: 21 Apr 2023 09:43
URI: https://eprints.iisc.ac.in/id/eprint/81321

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