New Biochemical Principles for NLR Immunity in Plants.

While working for the United States Department of Agriculture on the North Dakota Agricultural College campus in Fargo, North Dakota, in the 1940s and 1950s, Harold H. Flor formulated the genetic principles for coevolving plant host-pathogen interactions that govern disease resistance or susceptibility. His 'gene-for-gene' legacy runs deep in modern plant pathology and continues to inform molecular models of plant immune recognition and signaling. In this review, we discuss recent biochemical insights to plant immunity conferred by nucleotide-binding domain/leucine-rich-repeat (NLR) receptors, which are major gene-for-gene resistance determinants in nature and cultivated crops. Structural and biochemical analyses of pathogen-activated NLR oligomers (resistosomes) reveal how different NLR subtypes converge in various ways on calcium (Ca2+) signaling to promote pathogen immunity and host cell death. Especially striking is the identification of nucleotide-based signals generated enzymatically by plant toll-interleukin 1 receptor (TIR) domain NLRs. These small molecules are part of an emerging family of TIR-produced cyclic and noncyclic nucleotide signals that steer immune and cell-death responses in bacteria, mammals, and plants. A combined genetic, molecular, and biochemical understanding of plant NLR activation and signaling provides exciting new opportunities for combatting diseases in crops. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.