8XUO

Cryo-EM structure of tomato NRC2 dimer

8XUO の概要

• エントリーDOI: 10.2210/pdb8xuo/pdb
• EMDBエントリー: 38679
• 分子名称: NRC2, ADENOSINE-5'-DIPHOSPHATE, INOSITOL HEXAKISPHOSPHATE (3 entities in total)
• 機能のキーワード: tomato, helper nlr, dimer, plant protein
• 由来する生物種: Solanum lycopersicum (tomato)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 174709.66

構造登録者

Sun, Y.,Ma, S.C.,Chai, J.J. (登録日: 2024-01-13, 公開日: 2024-05-22, 最終更新日: 2024-09-04)

主引用文献

Ma, S.,An, C.,Lawson, A.W.,Cao, Y.,Sun, Y.,Tan, E.Y.J.,Pan, J.,Jirschitzka, J.,Kummel, F.,Mukhi, N.,Han, Z.,Feng, S.,Wu, B.,Schulze-Lefert, P.,Chai, J.
Oligomerization-mediated autoinhibition and cofactor binding of a plant NLR.
Nature, 632:869-876, 2024

PubMed Abstract: Nucleotide-binding leucine-rich repeat (NLR) proteins play a pivotal role in plant immunity by recognizing pathogen effectors. Maintaining a balanced immune response is crucial, as excessive NLR expression can lead to unintended autoimmunity. 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-activation. 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 (IP) or pentakisphosphate (IP) 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.

PubMed: 38866053
DOI: 10.1038/s41586-024-07668-7

実験手法

ELECTRON MICROSCOPY (2.84 Å)