Captured Protein Folding Structure... Funnel-Shaped Folding Hypothesis Proven

By applying time-resolved X-ray scattering, the folding process of cytochrome protein was elucidated. Through this, the funnel-shaped folding hypothesis, which had been proposed only as a theoretical model, was experimentally verified.

[Asia Economy Reporter Hwang Junho] Domestic researchers have succeeded in elucidating the protein folding process at the molecular level. This technology is expected to contribute to drug development based on protein structures.

The research team led by Professor Lee Hyochul of the Department of Chemistry at the Korea Advanced Institute of Science and Technology (KAIST) announced on the 9th that they have succeeded for the first time in the world in real-time observation of protein structural changes during the protein folding pathway, and the related paper was published in the Proceedings of the National Academy of Sciences of the United States of America.

The research team observed the protein folding process using a high-speed serial imaging technique with X-ray pulses. By continuously capturing the structural changes of proteins, they succeeded in revealing the series of protein folding processes at the molecular level.

The structure of a protein is determined by the sequence of amino acids and attains its unique structure through a specific folding process. However, if it folds incorrectly, the protein may fail to perform its normal functions. In such cases, diseases such as Alzheimer's, mad cow disease, and Parkinson's disease can occur. Accordingly, research on protein folding has been ongoing, but this is the first time the folding process has been observed in real time.

Professor Lee Hyo-cheol (from the left), Professor Lee Young-min, Researcher Kim Tae-woo

Through this study, the research team elucidated the folding process of cytochrome protein from a three-dimensional structural perspective. The team evaluated that they experimentally verified the funnel-shaped folding hypothesis, which theoretically proposed that an extremely diverse range of unfolded structures proceed to their unique folded structures.

Notably, they discovered that the speed of the folding process is not the commonly known exponential function form but a stretched exponential function form. The research team stated, "We experimentally found that the pathways from the unfolded protein to the folded state are very diverse."

First author Researcher Kim Taewoo expressed, "Protein folding is the most important biological phenomenon in forming three-dimensional protein structures, and understanding the folding process will be the foundation for protein structure-based drug development."

Professor Lee Youngmin of the KAIST Department of Chemistry, who participated as a co-corresponding author, emphasized, "Experimental verification of protein folding theoretical models will be an important asset for developing more accurate computational methods from the perspective of theoretical biophysics."