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Rice expressing the Pi-ta gene is resistant to strains of the rice blast fungus, Magnaporthe grisea, expressing AVR-Pita in a gene-for-gent relationship. Pi-ta encodes a putative cytoplasmic receptor with a centrally localized nucleotide-binding site and leucine-rich domain (LRD) at the C-terminus. AVR-Pita is predicted to encode a metalloprotease with an N-terminal secretary signal and pro-protein sequences. AVR-Pita176 lacks the secretary and proprotein sequences. We report here that transient expression of AVR-Pita176 inside plant cells results in a Pi-ta-dependent resistance response. AVR-Pita176 protein is shown to bind specifically to the LRD of the Pi-ta protein, both in the yeast two-hybrid system and in an in vitro binding assay. Single amino acid substitutions in the Pi-ta LRD or in the AVR-Pita176 protease motif that result in loss of resistance in the plant also disrupt the physical interaction, both in yeast and in vitro. These data suggest that the AVR-Pita176 protein binds directly to the Pi-ta LRD region inside the plant cell to initiate a Pi-ta-mediated defense response. [ABSTRACT FROM AUTHOR]