title: Structural and functional analysis of a plant resistance protein TIR domain reveals interfaces for self-association, signaling, and autoregulation.
abstract: The Toll/interleukin-1 receptor (TIR) domain occurs in animal and plant immune receptors. In the animal Toll-like receptors, homodimerization of the intracellular TIR domain is required for initiation of signaling cascades leading to innate immunity. By contrast, the role of the TIR domain in cytoplasmic nucleotide-binding/leucine-rich repeat (NB-LRR) plant immune resistance proteins is poorly understood. L6 is a TIR-NB-LRR resistance protein from flax (Linum usitatissimum) that confers resistance to the flax rust phytopathogenic fungus (Melampsora lini). We determine the crystal structure of the L6 TIR domain and show that, although dispensable for pathogenic effector protein recognition, the TIR domain alone is both necessary and sufficient for L6 immune signaling. We demonstrate that the L6 TIR domain self-associates, most likely forming a homodimer. Analysis of the structure combined with site-directed mutagenesis suggests that self-association is a requirement for immune signaling and reveals distinct surface regions involved in self-association, signaling, and autoregulation.
authors.affiliation: CSIRO Plant Industry, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Maud
authors.initials: M
authors.lastname: Bernoux
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Infectious Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ve
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Infectious Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Williams
authors.affiliation: CSIRO Plant Industry, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Warren
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Hatters
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Infectious Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Eugene
authors.initials: E
authors.lastname: Valkov
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Infectious Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: CSIRO Plant Industry, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Ellis
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Infectious Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia. Electronic address: b.kobe@uq.edu.au.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
authors.affiliation: CSIRO Plant Industry, Canberra, Australian Capital Territory 2601, Australia. Electronic address: peter.dodds@csiro.au.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Dodds
mesh_terms: D000595:Amino Acid Sequence; D001487:Basidiomycota; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019597:Flax / Q000276:immunology* / Q000382:microbiology; D006706:Homeostasis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010935:Plant Diseases / Q000276:immunology; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: C095731:L6 protein, Linum usitatissimum; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins