Oligomerization-mediated autoinhibition and cofactor binding of a plant NLR

Shoucai Ma (), Chunpeng An, Aaron W. Lawson, Yu Cao, Yue Sun, Eddie Yong Jun Tan, Jinheng Pan, Jan Jirschitzka, Florian Kümmel, Nitika Mukhi, Zhifu Han, Shan Feng, Bin Wu, Paul Schulze-Lefert () and Jijie Chai ()
Additional contact information
Shoucai Ma: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine
Chunpeng An: Max Planck Institute for Plant Breeding Research
Aaron W. Lawson: Max Planck Institute for Plant Breeding Research
Yu Cao: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine
Yue Sun: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine
Eddie Yong Jun Tan: Nanyang Technological University
Jinheng Pan: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine
Jan Jirschitzka: University of Cologne
Florian Kümmel: Max Planck Institute for Plant Breeding Research
Nitika Mukhi: Max Planck Institute for Plant Breeding Research
Zhifu Han: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine
Shan Feng: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine
Bin Wu: Nanyang Technological University
Paul Schulze-Lefert: Max Planck Institute for Plant Breeding Research
Jijie Chai: School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine

Nature, 2024, vol. 632, issue 8026, 869-876

Abstract: Abstract Nucleotide-binding leucine-rich repeat (NLR) proteins play a pivotal role in plant immunity by recognizing pathogen effectors1,2. Maintaining a balanced immune response is crucial, as excessive NLR expression can lead to unintended autoimmunity3,4. Unlike most NLRs, the plant NLR required for cell death 2 (NRC2) belongs to a small NLR group characterized by constitutively high expression without self-activation5. The mechanisms underlying NRC2 autoinhibition and activation are not yet understood. Here we show that Solanum lycopersicum (tomato) NRC2 (SlNRC2) forms dimers and tetramers and higher-order oligomers at elevated concentrations. Cryo-electron microscopy shows an inactive conformation of SlNRC2 in these oligomers. Dimerization and oligomerization not only stabilize the inactive state but also sequester SlNRC2 from assembling into an active form. Mutations at the dimeric or interdimeric interfaces enhance pathogen-induced cell death and immunity in Nicotiana benthamiana. The cryo-electron microscopy structures unexpectedly show inositol hexakisphosphate (IP6) or pentakisphosphate (IP5) bound to the inner surface of the C-terminal leucine-rich repeat domain of SlNRC2, as confirmed by mass spectrometry. Mutations at the inositol phosphate-binding site impair inositol phosphate binding of SlNRC2 and pathogen-induced SlNRC2-mediated cell death in N. benthamiana. Our study indicates a negative regulatory mechanism of NLR activation and suggests inositol phosphates as cofactors of NRCs.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07668-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:632:y:2024:i:8026:d:10.1038_s41586-024-07668-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07668-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().