KAIST

<Professor Ji-Joon Song of the KAIST Department of Biological Sciences>

Plants, with their unique immune systems, sometimes launch 'autoimmune responses' by mistakenly identifying their own protein structures as pathogens. In particular, 'hybrid necrosis,' a phenomenon where descendant plants fail to grow healthily and perish after cross-breeding different varieties, has long been a difficult challenge for botanists and agricultural researchers. In response, an international research team has successfully elucidated the mechanism inducing plant autoimmune responses and proposed a novel strategy for cultivar improvement that can predict and avoid these reactions.

Professor Ji-Joon Song's research team at KAIST, in collaboration with teams from the National University of Singapore (NUS) and the University of Oxford, announced on the 21st of July that they have elucidated the structure and function of the 'DM3' protein complex, which triggers plant autoimmune responses, using cryo-electron microscopy (Cryo-EM) technology.

This research is drawing attention because it identifies defects in protein structure as the cause of hybrid necrosis, which occurs due to an abnormal reaction of immune receptors during cross-breeding between plant hybrids.

This protein (DM3) is originally an enzyme involved in the plant's immune response, but problems arise when the structure of the DM3 protein is damaged in a specific protein combination called 'DANGEROUS MIX (DM)'.

Notably, one variant of DM3, the 'DM3Col-0' variant, forms a stable complex with six proteins and is recognized as normal, thus not triggering an immune response. In contrast, another 'DM3Hh-0' variant has improper binding between its six proteins, causing the plant to recognize it as an 'abnormal state' and trigger an immune alarm, leading to autoimmunity.

The research team visualized this structure using atomic-resolution cryo-electron microscopy (Cryo-EM) and revealed that the immune-inducing ability is not due to the enzymatic function of the DM3 protein, but rather to 'differences in protein binding affinity.'

<Figure 1. Mechanism of Plant Autoimmunity Triggered by the Collapse of the DM3 Protein Complex>

This demonstrates that plants can initiate an immune response by recognizing not only 'external pathogens' but also 'internal protein structures' when they undergo abnormal changes, treating them as if they were pathogens.

The study shows how sensitively the plant immune system changes and triggers autoimmune responses when genes are mixed and protein structures change during the cross-breeding of different plant varieties. It significantly advanced the understanding of genetic incompatibility that can occur during natural cross-breeding and cultivar improvement processes.

Dr. Gijeong Kim, the co-first author, stated, "Through international research collaboration, we presented a new perspective on understanding the plant immune system by leveraging the autoimmune phenomenon, completing a high-quality study that encompasses structural biochemistry, genetics, and cell biological experiments."

Professor Ji-Joon Song of the KAIST Department of Biological Sciences, who led the research, said, "The fact that the immune system can detect not only external pathogens but also structural abnormalities in its own proteins will set a new standard for plant biotechnology and crop breeding strategies. Cryo-electron microscopy-based structural analysis will be an important tool for understanding the essence of gene interactions."

This research, with Professor Ji-Joon Song and Professor Eunyoung Chae of the University of Oxford as co-corresponding authors, Dr. Gijeong Kim (currently a postdoctoral researcher at the University of Zurich) and Dr. Wei-Lin Wan of the National University of Singapore as co-first authors, and Ph.D candidate Nayun Kim, as the second author, was published on July 17th in Molecular Cell, a sister journal of the international academic journal Cell.

This research was supported by the KAIST Grand Challenge 30 project.

Article Title: Structural determinants of DANGEROUS MIX 3, an alpha/beta hydrolase that triggers NLR-mediated genetic incompatibility in plants DOI: https://doi.org/10.1016/j.molcel.2025.06.021