Targeted stabilization of MYC2 protein: AI-driven resistance design conquers citrus Huanglongbing

Citrus Huanglongbing (HLB), caused by the unculturable pathogen Candidatus Liberibacter asiaticus (CLas), poses a severe threat to the global citrus industry. This study reveals for the first time the molecular mechanism of the E3 ubiquitin ligase PUB21 as a core susceptibility gene, demonstrating its role in weakening plant immunity by ubiquitination-mediated degradation of the defense transcription factor MYC2. A natural dominant-negative mutant, PUB21DN, identified in resistant relatives, blocks MYC2 degradation and confers complete HLB resistance. A 14-amino acid peptide, APP3-14, screened via artificial intelligence (AI), stabilizes MYC2 through dual mechanisms and directly lyses CLas, reducing bacterial titers by over 90% in field trials. The study further elucidates the pathogen strategy of the CLas effector SDE5, which accelerates immune suppression by enhancing PUB21-MYC2 interaction. This work establishes a novel paradigm for HLB-resistant breeding and unculturable pathogen control through targeted protein stabilization.