NLR sensors meet at the SGT1–HSP90 crossroad

The NLR (nucleotide-binding domain and leucine-rich repeat containing) proteins provide pathogen-sensing systems that are conserved in both plants and animals. They can be activated directly or indirectly by pathogen-derived molecules through mechanisms that remain largely elusive. Studies in plants revealed that the molecular chaperone, HSP90, and its co-chaperones, SGT1 and RAR1, are major stabilizing factors for NLR proteins. More recent work indicates that SGT1 and HSP90 are also required for the function of NLR proteins in mammals, underscoring the evolutionary conservation of innate immune system regulatory mechanisms. Comparative analyses of plant and mammalian NLR proteins, together with recent insights provided by the structure of SGT1–HSP90 complex, have begun to uncover the mechanisms by which immune NLR sensors are regulated. The NLR (nucleotide-binding domain and leucine-rich repeat containing) proteins provide pathogen-sensing systems that are conserved in both plants and animals. They can be activated directly or indirectly by pathogen-derived molecules through mechanisms that remain largely elusive. Studies in plants revealed that the molecular chaperone, HSP90, and its co-chaperones, SGT1 and RAR1, are major stabilizing factors for NLR proteins. More recent work indicates that SGT1 and HSP90 are also required for the function of NLR proteins in mammals, underscoring the evolutionary conservation of innate immune system regulatory mechanisms. Comparative analyses of plant and mammalian NLR proteins, together with recent insights provided by the structure of SGT1–HSP90 complex, have begun to uncover the mechanisms by which immune NLR sensors are regulated.