Oligomerization-mediated autoinhibition and cofactor binding of a plant NLR

• 成果类型: Article
• 署名作者: Ma, Shoucai; An, Chunpeng; Lawson, Aaron W.; Cao, Yu; Sun, Yue; Tan, Eddie Yong Jun; Pan, Jinheng; Jirschitzka, Jan; Kuemmel, Florian; Mukhi, Nitika; Han, Zhifu; Feng, Shan; Wu, Bin; Schulze-Lefert, Paul; Chai, Jijie
• 署名单位: Westlake Laboratory; Westlake University; Xianghu Laboratory; Max Planck Society; Nanyang Technological University; University of Cologne; Max Planck Society
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5462
• DOI: 10.1038/s41586-024-07668-7
• 发表日期: 2024-08-22
• 关键词: resistance; hr; expression; help

摘要

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 Nicotianabenthamiana. 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. Cryo-electron microscopy reveals that the tomato immune receptor NRC2 forms oligomers to stabilize its inactive state and sequester it from activation, with inositol phosphates acting as immunoregulatory cofactors.