Ji-Joon+Song
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Why Do Plants Attack Themselves? The Secret of Genetic Conflict Revealed
<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
2025.07.21 View 427 -
Establishing a novel strategy to tackle Huntington’s disease
A platform to take on the Huntington’s disease via an innovative approach established by KAIST’s researchers through international collaboration with scientists in the Netherlands, France, and Sweden.
Through an international joint research effort involving ProQR Therapeutics of the Netherlands, Université Grenoble Alpes of France, and KTH Royal Institute of Technology of Sweden, Professor Ji-Soon Song's research team in the Department of Biological Sciences and KAIST Institute for BioCentury of KAIST, established a noble strategy to treat Huntington's disease. The new works showed that the protein converted from disease form to its disease-free form maintains its original function, providing new roadblocks to approach Huntington’s disease.
This research, titled, “A pathogenic-proteolysis resistant huntingtin isoform induced by an antisense oligonucleotide maintains huntingtin function”, co-authored by Hyeongju Kim, was published in the online edition of 'Journal of Clinical Investigation Insight' on August 9, 2022.
Huntington's disease is a dominantly inherited neurodegenerative disease and is caused by a mutation in a protein called ‘huntingtin’, which adds a distinctive feature of an expanded stretch of glutamine amino acids called polyglutamine to the protein. It is estimated that one in every 10,000 have Huntington's disease in United States. The patients would suffer a decade of regression before death, and, thus far, there is no known cure for the disease.
The cleavage near the stretched polyglutamine in mutated huntingtin is known to be the cause of the Huntington’s disease. However, as huntingtin protein is required for the development and normal function of the brain, it is critical to specifically eliminate the disease-causing protein while maintaining the ones that are still normally functioning.
The research team showed that huntingtin delta 12, the converted form of huntingtin that is resistant to developing cleavages at the ends of the protein, the known cause of the Huntington’s disease (HD), alleviated the disease’s symptoms while maintaining the functions of normal huntingtin.
Figure. Huntington's disease resistance huntingtin protein induced by antisense oligonucleotide (AON) is resistant to Caspase-6 cleavage, therefore, does not cause Huntington’s disease while maintaining normal functions of huntingtin.
The research was welcomed as it is sure to fuel innovate strategies to tackle Huntington’s disease without altering the essential function of huntingtin.
This work was supported by a Global Research Lab grant from the National Research Foundation of Korea (NRF) and by a EUREKA Eurostars 2 grant from European Union Horizon 2020.
2022.09.02 View 8888 -
Scientists Discover the Mechanism of DNA High-Order Structure Formation
(Molecular structures of Abo1 in different energy states (left), Demonstration of an Abo1-assisted histone loading onto DNA by the DNA curtain assay. )
The genetic material of our cells—DNA—exists in a high-order structure called “chromatin”. Chromatin consists of DNA wrapped around histone proteins and efficiently packs DNA into a small volume. Moreover, using a spool and thread analogy, chromatin allows DNA to be locally wound or unwound, thus enabling genes to be enclosed or exposed. The misregulation of chromatin structures results in aberrant gene expression and can ultimately lead to developmental disorders or cancers. Despite the importance of DNA high-order structures, the complexity of the underlying machinery has circumvented molecular dissection.
For the first time, molecular biologists have uncovered how one particular mechanism uses energy to ensure proper histone placement onto DNA to form chromatin. They published their results on Dec. 17 in Nature Communications.
The study focused on proteins called histone chaperones. Histone chaperones are responsible for adding and removing specific histones at specific times during the DNA packaging process. The wrong histone at the wrong time and place could result in the misregulation of gene expression or aberrant DNA replication. Thus, histone chaperones are key players in the assembly and disassembly of chromatin.
“In order to carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts that prevent histone aggregation and undesired interactions,” said Professor Ji-Joon Song in the Department of Biological Sciences at KAIST. “We set out to understand how a unique histone chaperone uses chemical energy to assemble or disassemble chromatin.”
Song and his team looked to Abo1, the only known histone chaperone that utilizes cellular energy (ATP). While Abo1 is found in yeast, it has an analogous partner in other organisms, including humans, called ATAD2. Both use ATP, which is produced through a cellular process where enzymes break down a molecule’s phosphate bond. ATP energy is typically used to power other cellular processes, but it is a rare partner for histone chaperones.
“This was an interesting problem in the field because all other histone chaperones studied to date do not use ATP,” Song said.
By imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain assay, the researchers could examine the protein interactions at the single-molecule level. The technique allows scientists to arrange the DNA molecules and proteins on a single layer of a microfluidic chamber and examine the layer with fluorescence microscopy.
The researchers found through real-time observation that Abo1 is ring-shaped and changes its structure to accommodate a specific histone and deposit it on DNA. Moreover, they found that the accommodating structural changes are powered by ADP.
“We discovered a mechanism by which Abo1 accommodates histone substrates, ultimately allowing it to function as a unique energy-dependent histone chaperone,” Song said. “We also found that despite looking like a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate chromatin assembly.”
The researchers plan to continue exploring how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapeutics that can target cancer-causing misbehavior by Abo1’s analogous human counterpart, ATAD2.
-Profile
Professor Ji-Joon Song
Department of Biological Sciences KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
2020.01.07 View 12832