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AIST Press Release
Discovery that Proteins Denature and Become Smaller
-A New Normal for Proteins, Expected to be Applied to Stabilization Technology for Antibody Drugs

Presenters:
Hiroshi Imamura, Assistant Professor, Nagahama Institute of Bio-Science and Technology
Shinya Honda, Invited Researcher, Biomedical Research Institute

Overview:
It has been believed that when a protein is denatured, the size of the molecule increases without exception. However, we have discovered that there are proteins whose radius of gyration decreases after denaturation, overturning this textbook common sense. This protein was an antibody (immunoglobulin G), which is very important for both research and medical applications.
Using a new analytical method called "size-exclusion chromatography coupled small-angle X-ray scattering (SEC-SAXS)," the researchers found that when the antibody was immersed in acid, it changed from its natural Y-shaped structure to a smaller spherical structure. Unable to explain this phenomenon using conventional empirical rules in protein science, Dr. Honda and his team proposed a new model to interpret this phenomenon. This research is an important achievement in protein science because the model indicates that the same thing can happen with other large proteins (multi-domain proteins) other than antibodies. Although the biological significance of antibodies that denature and become smaller is not fully clear, it is thought to be related to improved digestion tolerance in the stomach (promoting passive immunity) and secretion from antibody-producing cells (increasing productivity).
Details of the research results were published on April 24, 2023 in The Journal of Physical Chemistry Letters, a journal published by the American Chemical Society.

Please click here (Japanese) to read the detailed press release article.

Shinya Honda

Shodai Hino, Norioki Kawasaki, and Atsuyoshi Nakayama of the Biomolecule Design Research Group received the Interesting Panel Award for their panel "Degradation Control of Biodegradable Plastic by Light" exhibited at the Industrial Technology Support Fair in KANSAI 2022 - Manufacturing x "Power for Life" held at the Business Innovation Center Osaka on November 11, 2022.

Panel title: Control of Degradation of Biodegradable Plastics by Light
Presenters:
Biomolecule Design Research Group, Biomedical Research Institute
Shodai Hino, Norioki Kawasaki, Atsuyoshi Nakayama

Research results of Tomoki Himiyama, Biomolecule Design Research Group, have been published in Bioconjugate Chemistry and selected for the Supplementary Cover.

Paper:
Himiyama, T., Hamaguchi, T., Yonekura, K., Nakamura, T.: Unnaturally Distorted Hexagonal Protein Ring Alternatingly Reorganized from Two Distinct Chemically Modified Proteins. Bioconjugate Chem., 34(4), 764-774 (2023).　
Details

Abstract of Results:
Modifications of protein assembly states and shapes were achieved by chemical modification. Two types of dissociating mutants were designed by introducing amino acid mutations to the hexagonal ring-type protein assembly. Subsequent chemical modifications reconstructed the protein-protein interactions to reorganize them into an artificial assembly composed of two types of mutants. Cryo-electron microscopy measurements by Dr. Tasuku Hamaguchi (Associate Professor at Tohoku University) and Dr. Koji Yonekura (Group Director/Professor at RIKEN/Tohoku University) revealed that this artificial protein assembly has a unique shape that is distorted from the regular hexagon of the wild-type protein, and that the two mutants are arranged alternately. This research has enabled the construction of artificial protein assemblies, which have been difficult to access with conventional amino acid mutations. Details of this technique were published in Bioconjugate Chemistry on April 19, 2023, and this paper was selected for the Supplementary Cover.

Michiyo Maruyama, Molecular Neurobiology Research Group

My name is Michiyo Maruyama and I am assigned to the Molecular Neurobiology Research Group. When I was a student, I studied how living organisms sense seasonal changes and adapt to their environment. This is a topic that goes to the root of the mechanisms of life phenomena, but in fact, the reason I became interested in this research was because I wanted to solve the problem of "winter depression," which is a depressed mood during the winter season. I am sure that everyone feels the seasonal change in mental state, such as "I feel somewhat depressed in winter" and "I feel fine when spring comes”. I am one of those who have felt these changes, and I have been studying the mechanism of seasonal sensing, thinking that if the mechanism of sensing the seasons could be clarified, it would contribute to solving the problem of winter depression.
I would like to conduct research on premenstrual syndrome (PMS), a condition in which women become irritable and depressed during the premenstrual period, and we believe that PMS is also a problem that many women (and men around them) suffer from. I would like to conduct research with people from various fields to find out how PMS is caused, what kind of people are prone to PMS, and if there are any methods of alleviating PMS that are easier to use and have fewer side effects than the medication currently available at hospitals. I know that there are still many things I am not up to speed on, but I look forward to your guidance and encouragement.

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