Hidden route of protein damage through oxygen-confined photooxidation
Oxidative modifications can disrupt protein folds and functions, and are strongly associated with human aging and diseases. Conventional oxidation pathways typically involve the free diffusion of reactive oxygen species (ROS), which primarily attack the protein surface. Yet, it remains unclear whether and how internal protein folds capable of trapping oxygen (O<sub>2</sub>) contribute to oxidative damage. Here, we report a hidden pathway of protein damage, which we refer to as O<sub>2</sub>-confined photooxidation. In this process, O<sub>2</sub> is captured in protein cavities and subsequently converted into multiple ROS, primarily mediated by tryptophan residues under blue light irradiation. The generated ROS then attack the protein interior through constrained diffusion, causing protein damage. The effects of this photooxidative reaction appear to be extensive, impacting a wide range of cellular proteins, as supported by whole-cell proteomic analysis. This photooxidative mechanism may represent a latent oxidation pathway in human tissues directly exposed to visible light, such as skin and eyes.
Authors
- Gwangsu Yoon (ORCID: https://orcid.org/0000-0002-1900-6504)
- Duyoung Min (ORCID: https://orcid.org/0000-0002-2856-8082)
- Chae Un Kim (ORCID: https://orcid.org/0000-0001-9350-8441)
- Eunhye Hwang (ORCID: https://orcid.org/0000-0003-2036-551X)
- Kyungjae Myung (ORCID: https://orcid.org/0000-0001-7975-6190)
- Tae‐Hyuk Kwon (ORCID: https://orcid.org/0000-0002-1633-6065)
- Seung Kyu Min (ORCID: https://orcid.org/0000-0001-5636-3407)
- Mingyu Park (ORCID: https://orcid.org/0000-0003-2958-3978)
- Yu‐Gon Eom (ORCID: https://orcid.org/0000-0002-9563-5169)
- Seoyoon Kim
- Jeong‐Mo Choi (ORCID: https://orcid.org/0000-0003-2656-4851)
- Chaiheon Lee (ORCID: https://orcid.org/0000-0002-3824-8410)
- Seungjin Na (ORCID: https://orcid.org/0000-0002-5159-2048)
- Victor W. Sadongo
- Seong Ho Kim (ORCID: https://orcid.org/0000-0002-5844-0354)
- Byung‐Gyu Kim (ORCID: https://orcid.org/0000-0002-1152-4542)
- W.C. Bhashini Wijesinghe
- Eojin Kim
- Hannah Jeong
Institutions
- Institute for Basic Science (KR)
- Korea Basic Science Institute (KR)
- Ulsan National Institute of Science and Technology (KR)
- Pusan National University (KR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-55168-z
- Citations
- 19
- Primary Topic
- Hemoglobin structure and function
- Type
- article
- Field-Weighted Citation Impact
- 6.19
Funders
- POSCO TJ Park Foundation
- National Research Foundation
- National Cancer Center
- Korea Basic Science Institute
- National Research Foundation of Korea
- Institute for Basic Science