Available online at www.sciencedirect.com STANDing strong, resistance proteins instigators of plant defence Ewa Lukasik and Frank LW Takken Resistance (R) proteins are involved in specific pathogen recognition and subsequent initiation of host defence. Most R proteins are nucleotide binding – leucine rich repeat (NB–LRR) proteins, which form a subgroup within the STAND (signal transduction ATPases with numerous domains) family. Activity of these multi-domain proteins depends on their ability to bind and hydrolyse nucleotides. Since R protein activation often triggers cell-death tight regulation of activation is essential. Autoinhibition, which seems to be accomplished by intramolecular interactions between the various domains, is important to retain R proteins inactive. This review summarizes recent data on intra- and intermolecular interactions that support a model in which pathogen perception triggers a series of conformational changes, allowing the newly exposed NB domain to interact with downstream signalling partners and activate defence signalling. Addresses Plant Pathology, Swammerdam Institute for Life Sciences, University of Amsterdam, PO Box 94215, 1090 GE Amsterdam, The Netherlands Corresponding author: Takken, Frank LW (f.l.w.takken@uva.nl) Current Opinion in Plant Biology 2009, 12:427–436 This review comes from a themed issue on Biotic Interactions Edited by Xinnian Dong and Regine Kahmann Available online 24th April 2009 1369-5266/$ – see front matter # 2009 Elsevier Ltd. All rights reserved. DOI 10.1016/j.pbi.2009.03.001 Introduction The long history of battle between pathogens and plants is evident by the sophisticated, multilayered immune system of plants [1]. The first line of the innate defence system is based on recognition of con- served pathogen-derived molecules, called MAMPs (microbe- associated molecular patterns), by pattern recognition receptors (PRR). Specialized microbes, however, can evade or suppress this MAMP triggered immunity (MTI) by secretion of virulence factors, so- called effectors. A subset of these effectors, referred to as AVRs, can be perceived by resistance (R) proteins that trigger a second layer of host defence, referred to as effector triggered immunity (ETI). Rapid ion fluxes, an oxidative burst, and transcriptional reprogramming are induced during both MTI and ETI. Only with the latter often also programmed cell death around the infection site occurs, which is called the hypersensitive response (HR). The complex relation between plant resistance and pathogen virulence through co-evolution was recently described as a ‘zig-zag’ model [1]. An illustrative example of this zig-zag model is the interaction between tomato and Fusarium oxysporum. The fungus requires the effector AVR3 for full virulence, possibly to sup- press MTI. This effector, however, can be recognized by the tomato R protein I-3 that subsequently triggers ETI. To counteract this defence response, it has been hypothesized that the fungus evolved a second effector (AVR1) that suppresses these I-3 mediated defences. To thwart the fungus the plant in turn evolved R protein I-1 that recognizes AVR1 and activates host defences once more [2  ]. Over 40 R genes have been cloned over the last two decades and the majority belongs to the NB–LRR family, as they contain a nucleotide-binding domain (NB) fused to a C-terminal leucine-rich repeat (LRR) domain (Figure 1). The LRR domain is proposed to adopt an arc-shaped conformation, forming a protein-protein inter- action surface [3]. The NB is part of a larger domain that is called the NB–ARC as it is shared between R proteins and the human apoptotic protease-activating factor 1 (APAF-1) and its Caenorhabditis elegans homolog CED- 4. As indicated in Figure 1, many conserved motifs can be discerned in the NB–ARC domain. Proteins carrying an NB–ARC domain belong to the STAND (signal trans- duction ATPases with numerous domains) family of NTPases [4]. Based on 3D modelling, the NB–ARC of R proteins is proposed to contain three subdomains: the NB forming a P-loop NTPase fold, the ARC1 consisting of a four-helix bundle and the ARC2 adopting a winged-helix fold (reviewed in [5]; Figure 1). Most of the conserved motifs in the NB–ARC are present at the interface of these three domains where they form the nucleotide-binding pocket (Figure 1). The N-termini of NB–LRRs are structurally diverse. Some carry a domain having homology to the toll and human interleukin-1 receptor (TIR) domain and these R proteins are called TIR-NB–LRRs or TNLs. Non-TIR NB–LRR members are referred to as CC–NB– LRRs or CNLs, because many of them contain a pre- dicted coiled coil region (CC), sometimes extended by a DNA binding domain such as a BEAF/DREAF zinc finger domain (BED) or by a solanaceous domain (SD) (reviewed in [6]). www.sciencedirect.com Current Opinion in Plant Biology 2009, 12:427–436