Arabidopsis immunity regulator EDS1 in a PAD4/SAG101-unbound form is a monomer with an inherently inactive conformation.

•Enhanced disease susceptibility 1 (EDS1) is a central plant innate immunity regulator.•EDS1/nanobody crystal structures and EDS1 solution structures (SAXS) were determined.•Unbound from its functional heterodimerization partners, EDS1 is stable as a monomer.•An esterase catalytic triad of EDS1 is inactivated by features of the protein matrix.•The EDS1 monomer represents an inactive ground state to build activated complexes.