Hijacking the Host: Do SAP05-RPN10 interactions shape phytoplasma susceptibility in apple?

'Candidatus Phytoplasma mali', the bacterium associated with apple proliferation (AP) disease, alters its host Malus domestica by secreting effector proteins that tackle key regulatory processes in the plant. Several phytoplasma effectors target plant transcription factors (TFs), promoting their degradation and leading to characteristic symptoms such as witches’ broom, abnormal growth, and reduced fruit quality [1]. Among these effectors, SAP05 induces ubiquitin-independent proteasomal degradation of SPL and GATA TFs by hijacking the host 26S proteasomal subunit RPN10 [2, 3]. Effector-host interactions have been extensively studied in Arabidopsis thaliana, where structural advances and predictions have provided atomic-level insights into pathogen-driven cellular reprogramming [4]. These findings established a paradigm of targeted protein degradation and opened opportunities for innovative breeding strategies [5]. In this study, we focus on SAP05-mediated host manipulation across Malus species to elucidate the molecular basis of susceptibility and resistance, placing structural analysis of SAP05 in complex with RPN10 and SPL TFs at the core of our approach. High-resolution structures of these complexes will help resolving the atomic determinants of binding specificity and host range. Comparative analysis of SAP05 interactions with orthologous and paralogous RPN10 and TF variants across different apple species further defines the structural basis of effector specificity and links it to natural genetic diversity and resistance to phytoplasma infections. Building on this structural framework we assess whether sequence variation in rpn10 contributes to differential resistance between highly susceptible Malus domestica and partially resistant Malus sieboldii, a key genetic resource for resistance breeding. Single nucleotide variation (SNV) analysis of the von Willebrand A (vWA) domain across four identified rpn10 paralogs revealed variation in predicted SAP05-interacting and regulatory regions. These data, integrated with qPCR-based expression profiling, are used to resolve paralog-specific expression patterns, infer functional diversification, and relate host variation to susceptibility or tolerance to phytoplasma infection. By integrating structural analyses, this work provides a mechanistic basis for SAP05-driven host reprogramming in apple, revealing species-specific differences in phytoplasma susceptibility and supporting targeted strategies for disease management and resistance breeding. [1] Sugio et al. Annual Review of Phytopathology, 2011, 49:175–195.[2] Huang et al. Cell, 2021, 184, 5201 - 5214.e12.[3] Zhang et al. bioRxiv, 2024, 12;27(2):108892.[4] Mirkin et al. PLoS Genetics, 2025, 21, 11.[5] Yan et al. Nat. Commun. 2024, 15, 1170.