A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection

Aaron Whiteley — Tue, 17 Dec 2024 16:00:00 +0000

A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection Aaron Whiteley Tue, 12/17/2024 - 09:00

Emily Kibby , Laurel Robbins , Deep A , Min NK , Lindsay Whalen , Toni Nagy , Freeborn L , Corbett KD , Aaron Whiteley

BioRxiv (2024)

Abstract

Immune systems must rapidly sense viral infections to initiate antiviral signaling and protect the host. Bacteria encode >100 distinct viral (phage) defense systems and each has evolved to sense crucial components or activities associated with the viral lifecycle. Here we used a high-throughput AlphaFold-multimer screen to discover that a bacterial NLR-related protein directly senses multiple phage proteins, thereby limiting immune evasion. Phages encoded as many as 5 unrelated activators that were predicted to bind the same interface of a C-terminal sensor domain. Genetic and biochemical assays confirmed activators bound to the bacterial NLR-related protein at high affinity, induced oligomerization, and initiated signaling. This work highlights how in silico strategies can identify complex protein interaction networks that regulate immune signaling across the tree of life.

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Emily M. Kibby, Laurel K. Robbins, Amar Deep, Nathan K. Min, Lindsay A. Whalen, Toni A. Nagy, Layla Freeborn, Kevin D. Corbett, Aaron T. Whiteley. A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection. bioRxiv 2024.12.17.629029; doi: https://doi.org/10.1101/2024.12.17.629029

Kibby EM, Robbins LK, Deep A, Min NK, Whalen LA, Nagy TA, Freeborn L, Corbett KD, ➤Whiteley, AT | BioRxiv 2024

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A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection

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