Biochemical basis of activation and inhibition of an NLR immune receptor network

Contreras, Mauricio P (2023) Biochemical basis of activation and inhibition of an NLR immune receptor network. Doctoral thesis, University of East Anglia.

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The plant immune system employs intracellular nucleotide-binding domain and leucine-rich repeat (NLR) receptors to identify and respond to pathogen-derived virulence proteins, termed effectors. NLRs function individually or in configurations such as pairs or networks. In solanaceous plants, the NLR required for cell death (NRC) network mediates resistance against various pathogens. The molecular mechanisms by which the NRC network activates are not understood. Moreover, some pathogen effectors can suppress NLRs to promote virulence, and the mechanisms of this suppression are largely unknown.

In this thesis, I characterized a cell death-inducing truncation of the helper NRC4, leading to the identification of a conserved N-terminal motif in CC-NLRs. Using mutated NRC variants, I established a method for monitoring NRC activation and investigated sensor-helper communication in the NRC network. My findings support an activation and release model in which NRC-dependent sensors mediate oligomerization of helper NRCs without joining the helper oligomer. The NB domain can encode the minimal signal for resistosome formation in many NRC-dependent sensors.

I also elucidated the suppression mechanisms of AVRcap1b and SS15, two effectors that inhibit NRC2 and NRC3. AVRcap1b connects activated NRCs to host TOL proteins, suppressing immunity, while SS15 binds inactive NRCs, preventing helper activation and resistosome formation. Understanding the suppression mechanism enabled me to bioengineer NRC variants that evade inhibition. This work presents a model for sensor-helper activation of NLRs, provides insights into pathogen manipulation of NLR signaling, and demonstrates a novel strategy for bioengineering of disease resistance.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > The Sainsbury Laboratory
Depositing User: Chris White
Date Deposited: 26 Oct 2023 09:07
Last Modified: 26 Oct 2023 09:07

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