Polyamines Disrupt the KaiABC Oscillator by Inducing Protein Denaturation
Jinkui Li,
Lingya Zhang,
Junwen Xiong,
Xiyao Cheng,
Yongqi Huang,
Zhengding Su,
Ming Yi,
Sen Liu
Affiliations
Jinkui Li
Key Laboratory of Fermentation Engineering (HBUT, Ministry of Education) and National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
Lingya Zhang
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Medical College of China Three Gorges University, Yichang 443002, China
Junwen Xiong
Key Laboratory of Fermentation Engineering (HBUT, Ministry of Education) and National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
Xiyao Cheng
Key Laboratory of Fermentation Engineering (HBUT, Ministry of Education) and National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
Yongqi Huang
Key Laboratory of Fermentation Engineering (HBUT, Ministry of Education) and National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
Zhengding Su
Key Laboratory of Fermentation Engineering (HBUT, Ministry of Education) and National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
Ming Yi
School of Mathematics and Physics, China University of Geosciences, Wuhan 430074, China
Sen Liu
Key Laboratory of Fermentation Engineering (HBUT, Ministry of Education) and National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles in cells by stabilizing chromatin structure, regulating DNA replication, modulating gene expression, etc., and they also affect the structure and function of proteins. A few studies have investigated the impact of polyamines on protein structure and function previously, but no reports have focused on a protein-based biological module with a dedicated function. In this report, we investigated the impact of polyamines (putrescine, spermidine, and spermine) on the cyanobacterial KaiABC circadian oscillator. Using an established in vitro reconstitution system, we noticed that polyamines could disrupt the robustness of the KaiABC oscillator by inducing the denaturation of the Kai proteins (KaiA, KaiB, and KaiC). Further experiments showed that the denaturation was likely due to the induced change of the thermal stability of the clock proteins. Our study revealed an intriguing role of polyamines as a component in complex cellular environments and would be of great importance for elucidating the biological function of polyamines in future.
