Resistance proteins: molecular switches of plant defence Frank LW Takken 1 , Mario Albrecht 2 and Wladimir IL Tameling 3 Specificity of the plant innate immune system is often conferred by resistance (R) proteins. Most R proteins contain leucine-rich repeats (LRRs), a central nucleotide-binding site (NBS) and a variable amino-terminal domain. The LRRs are mainly involved in recognition, whereas the amino-terminal domain determines signalling specificity. The NBS forms part of a nucleotide binding (NB)-ARC domain that presumably functions as a molecular switch. The conserved nature of NB-ARC proteins makes it possible to map mutations of R protein residues onto the crystal structures of related NB-ARC proteins, providing hypotheses for the functional roles of these residues. A functional model emerges in which the LRRs control the molecular state of the NB-ARC domain. Pathogen recognition triggers nucleotide-dependent conformational changes that might induce oligomerisation, thereby providing a scaffold for activation of downstream signalling components. Addresses 1 Plant Pathology, Swammerdam Institute for Life Sciences, University of Amsterdam, PO Box 94062, 1090 GB Amsterdam, The Netherlands 2 Max Planck Institute for Informatics, Stuhlsatzenhausweg 85, 66123 Saarbru ¨ cken, Germany 3 The Sainsbury Laboratory, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK Corresponding author: Takken, Frank LW (f.l.w.takken@uva.nl) Current Opinion in Plant Biology 2006, 9:383–390 This review comes from a themed issue on Biotic interactions Edited by Anne Osbourn and Sheng Yang He Available online 19th May 2006 1369-5266/$ – see front matter # 2006 Elsevier Ltd. All rights reserved. DOI 10.1016/j.pbi.2006.05.009 Introduction To combat pathogens, plants have evolved a sophisti- cated, multilayered system of passive and active defence mechanisms. Except for the RNA-based anti- viral defence, which is a form of adaptive immunity, plants rely on an innate immune system [1  ,2]. Microbes disclose their presence to the host’s innate immune system through pathogen-associated molecular patterns (PAMPs). These PAMPs are evolutionary conserved molecules that are often indispensable for the microbe’s lifestyle [2]. They act as general elicitors that are recog- nized by the host via specialized PAMP receptors, triggering subsequent induction of ‘basal’ defence responses [2,3]. Many pathogens, however, have found ways to evade and/ or actively suppress the host’s basal defence responses, and hence have acquired the ability to cause plant dis- eases. To evade recognition, a pathogen might hide or alter a specific PAMP. For instance, Agrobacterium tume- faciens has a modified flagellin domain that can no longer be recognized by the Arabidopsis flagellin receptor [4]. Alternatively, pathogens might suppress basal defence responses using specific effector molecules [5]. One of the best-studied examples is the suppression of RIN4-regu- lated basal defence in Arabidopsis by the Pseudomonas syringae effector proteins AvrRpm1 and AvrRpt2 [6  ,7]. A drawback for the pathogen is that, by manipulating the host cell machinery, it risks triggering the activation of a second line of plant defence, called ‘gene-for-gene’ resis- tance. This type of resistance is based on the presence of specific resistance (R) genes that mediate the recognition of race-specific effectors (Avr proteins). The emerging picture is that R proteins monitor the integrity of com- ponents of the basal PAMP-recognition-based immune system. Perturbation of these components by effector/Avr proteins could trigger activation of the R protein. To elaborate on the RIN4 example given above, this Avr target, which plays a role in regulating basal defence, is ‘guarded’ by at least two different R proteins: RPM1 and RPS2. Phosphorylation of RIN4 in the presence of AvrRpm1 triggers RPM1 activation, whereas degradation of the RIN4 protein by AvRpt2 activates RPS2 [8–10]. In the latter case, AvrRpt2-mediated cleavage of RIN4 releases its association with RPS2, and thereby removes the negative regulation of RPS2 function by RIN4 [11]. Release of negative regulation triggers R-protein activa- tion, which results in the induction of rapid defence responses, frequently culminating in a hypersensitive response (recently reviewed in [1  ]). These examples provide a mechanistic link between basal and gene-for- gene resistance. If guarding the components of PAMP signalling pathways turns out to be the main function of R proteins [2,12  ], it would provide the plant with a robust immune system [6  ]. Numerous R proteins have been identified and the majority contain a nucleotide binding site (NBS) and a carboxy-terminal leucine-rich repeat (LRR) domain [13]. At the N-terminus, NBS-LRR proteins carry either a coiled coil (CC) domain (in CNL proteins) or a domain that has homology to the Toll/Interleukin-1 Receptor (TIR) domain (in TNL proteins) [14]. The N-terminal domain is thought to be involved in downstream signal- ling, whereas the LRRs seem to be the main determinant for recognition specificity [1  ,13]. The NBS is part of a larger domain, which is called nucleotide binding www.sciencedirect.com Current Opinion in Plant Biology 2006, 9:383–390