A novel innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins

Apte, Shruti ; Bhutda, Smita ; Ghosh, Sourav ; Sharma, Kuldeep ; Sahay, Osheen ; Rakshit, Jyotirmoy ; Sinha, Akash Raj ; Dibyachintan, Soham ; Roy, Suvapriya ; Datey, Akshay ; Santra, Shweta ; Joseph, Jincy ; Sasidharan, Sreeja ; Hammerschmidt, Sven ; Chakravortty, Dipshikha ; Santra, Manas ; Banerjee, Anirban (2021) A novel innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins Microbiology .

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Official URL: http://doi.org/10.1101/2021.10.20.465158

Related URL: http://dx.doi.org/10.1101/2021.10.20.465158

Abstract

Sensing of pathogens by ubiquitination is critical for maintaining cytosolic sanctity. However, universal ubiquitination targets on bacteria, especially of proteinaceous origin, remain unidentified. Here, we unveil a novel strategy, involving recognition of degron-like motifs for identification of first protein-based ubiquitination substrates on phylogenetically distinct bacteria. Such motifs can form a new class of intra-cytosolic pathogen associated molecular patterns (PAMPs) as their incorporation enables identification of non-ubiquitin targets by host Ub-ligases. We find SCFFBW7 E3-ligase, supported by the regulatory kinase, GSK3β, is crucial for effective pathogen detection and clearance. This may explain the enhanced risk of infections in Chronic Lymphocytic Leukaemia patients bearing FBXW7 mutations. We conclude that exploitation of such ubiquitous pathogen sensing strategy allows conservation of cellular resources and boost anti-microbial immunity.

Item Type:Article
Source:Copyright of this article belongs to bioRxiv
ID Code:133132
Deposited On:26 Dec 2022 11:27
Last Modified:02 Feb 2023 04:27

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