TY - JOUR TI - Effector target-guided engineering of an integrated domain expands the disease resistance profile of a rice NLR immune receptor AU - Maidment, Josephine HR AU - Shimizu, Motoki AU - Bentham, Adam R AU - Vera, Sham AU - Franceschetti, Marina AU - Longya, Apinya AU - Stevenson, Clare EM AU - De la Concepcion, Juan Carlos AU - Białas, Aleksandra AU - Kamoun, Sophien AU - Terauchi, Ryohei AU - Banfield, Mark J A2 - Zhou, Jian-Min A2 - Kleine-Vehn, Jürgen A2 - Zhou, Jian-Min A2 - Tao, Xiaorong VL - 12 PY - 2023 DA - 2023/05/18 SP - e81123 C1 - eLife 2023;12:e81123 DO - 10.7554/eLife.81123 UR - https://doi.org/10.7554/eLife.81123 AB - A subset of plant intracellular NLR immune receptors detect effector proteins, secreted by phytopathogens to promote infection, through unconventional integrated domains which resemble the effector’s host targets. Direct binding of effectors to these integrated domains activates plant defenses. The rice NLR receptor Pik-1 binds the Magnaporthe oryzae effector AVR-Pik through an integrated heavy metal-associated (HMA) domain. However, the stealthy alleles AVR-PikC and AVR-PikF avoid interaction with Pik-HMA and evade host defenses. Here, we exploited knowledge of the biochemical interactions between AVR-Pik and its host target, OsHIPP19, to engineer novel Pik-1 variants that respond to AVR-PikC/F. First, we exchanged the HMA domain of Pikp-1 for OsHIPP19-HMA, demonstrating that effector targets can be incorporated into NLR receptors to provide novel recognition profiles. Second, we used the structure of OsHIPP19-HMA to guide the mutagenesis of Pikp-HMA to expand its recognition profile. We demonstrate that the extended recognition profiles of engineered Pikp-1 variants correlate with effector binding in planta and in vitro, and with the gain of new contacts across the effector/HMA interface. Crucially, transgenic rice producing the engineered Pikp-1 variants was resistant to blast fungus isolates carrying AVR-PikC or AVR-PikF. These results demonstrate that effector target-guided engineering of NLR receptors can provide new-to-nature disease resistance in crops. KW - rice blast disease KW - plant immunity KW - protein engineering KW - NLR immune receptor JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -