Apte, Shruti, Bhutda, Smita, Ghosh, Sourav, Sharma, Kuldeep, Barton, Thomas E 
ORCID: 0000-0002-4592-4261, Dibyachintan, Soham, Sahay, Osheen, Roy, Suvapriya, Sinha, Akash Raj, Adicherla, Harikrishna et al (show 12 more authors)
(2023)
An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.
SCIENCE ADVANCES, 9 (12).
eade1851-.
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Abstract
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 SCF<sup>FBW7</sup> 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: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Bacteria, Bacterial Proteins, F-Box Proteins, Cell Cycle Proteins, Membrane Proteins, Phosphorylation, Ubiquitination, F-Box-WD Repeat-Containing Protein 7 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology > School of Life Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 Apr 2023 10:17 |
| Last Modified: | 10 May 2023 13:29 |
| DOI: | 10.1126/sciadv.ade1851 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169746 |
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