Plant NBS-LRR proteins in pathogen sensing and host defense

Abstract

Plant proteins belonging to the nucleotide-binding site-leucine-rich repeat (NBS-LRR) family are used for pathogen detection. Like the mammalian Nod-LRR protein 'sensors' that detect intracellular conserved pathogen-associated molecular patterns, plant NBS-LRR proteins detect pathogen-associated proteins, most often the effector molecules of pathogens responsible for virulence. Many virulence proteins are detected indirectly by plant NBS-LRR proteins from modifications the virulence proteins inflict on host target proteins. However, some NBS-LRR proteins directly bind pathogen proteins. Association with either a modified host protein or a pathogen protein leads to conformational changes in the amino-terminal and LRR domains of plant NBS-LRR proteins. Such conformational alterations are thought to promote the exchange of ADP for ATP by the NBS domain, which activates 'downstream' signaling, by an unknown mechanism, leading to pathogen resistance.

Figure 1

NBS domain structure and location of informative substitutions in plant NBS-LRR proteins. Top, a ‘stereo’ view of the mammalian Apaf-1 Nod domain crystal structure bound to ADP (Molecular Modeling Database accession number, 33022). Helical domain II is not included because of the lack of complementarily to plant NBS domains. Bottom, a ‘stereo’ view of the ADP-binding pocket of mammalian Apaf-1, including side chains involved in coordinating ADP binding. The ADP-binding pocket is defined by helical domain I (cyan), the α-β domain (blue) and the winged helix domain (magenta). Amino acid substitutions of plant NBS domain mutants are mapped onto the Apaf-1 structure; autoactivating substitutions are green and loss-of-function substitutions are red. The side chains for the corresponding residues are in those colors as well, except where those residues differ among plant and Apaf-1 sequences. Images produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by National Institutes of Health P41 RR-01081).

Figure 2

Model for plant NBS-LRR activation. Signaling is activated in a similar way for both direct (left) and indirect (right) modes of pathogen detection. Presence of the pathogen effector(1) alters the structure of the NBS-LRR protein through direct binding (left) or modification of additional plant proteins (right), allowing exchange of ADP for ATP. Binding of ATP to the NBS domain (2) results in activation of signal transduction through the creation of binding sites for downstream signaling molecules and/or the formation of NBS-LRR protein multimers. Dissociation of the pathogen effector and modified effector targets (if present; 3) along with hydrolysis of ATP (4) returns the NBS-LRR protein to its inactive state.