An evolutionarily conserved C4HC3-type E3 ligase regulates plant broad-spectrum resistance against pathogens

Deployment of broad-spectrum disease resistance against multiple pathogen species is an efficient way to control plant diseases. Here, we identify a Microtubule-associated C4HC3-type E3 Ligase (MEL) in both Nicotiana benthamiana and Oryza sativa, and show that it is able to integrate and initiate a series of host immune signaling, conferring broad-spectrum resistance to viral, fungal, and bacterial pathogens. We demonstrate that MEL forms homodimer through intermolecular disulfide bonds between its cysteine residues in the SWIM domain, and interacts with its substrate serine hydroxymethyltrasferase 1 (SHMT1) through the YφNL motif. Ubiquitin ligase activity, homodimerization and YφNL motif are indispensable for MEL to regulate plant immunity by mediating SHMT1 degradation through the 26S proteasome pathway. Our findings provide a fundamental basis for utilizing the MEL-SHMT1 module to generate broad-spectrum-resistant rice to global destructive pathogens including rice stripe virus, Magnaporthe oryzae, and Xanthomonas oryzae pv. oryzae.