Polyamines Disrupt the KaiABC Oscillator by Inducing Protein Denaturation.

Jinkui Li,Sen Liu,Xiyao Cheng,Junwen Xiong,Ming Yi,Lingya Zhang,Zhengding Su,Yongqi Huang

doi:10.3390/molecules24183351

Abstract

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.

Highlights

Polyamines are a kind of polycationic molecule which plays important roles in various cellular processes including stabilizing chromatin structure, regulating DNA replication, modulating gene expression, and interfering cell cycle [1]
The cellular concentration of putrescine was around 20-fold less than spermidine [3], so the reference concentration of putrescine in cyanobacterial cells was estimated to be around 400 μM. These concentrations are comparable to the polyamine concentrations in normal human cells which are up to millimolar ranges [20]
Molecules 2019, 24, x putrescine in cyanobacterial cells was estimated to be around 400 μM. These concentrations are comparable to the polyamine concentrations in normal human cells which are up to millimolar ranges contents in human cells quite contents different, and incells specific cells such and as tumor cells

Summary

Introduction

Polyamines are a kind of polycationic molecule which plays important roles in various cellular processes including stabilizing chromatin structure, regulating DNA replication, modulating gene expression, and interfering cell cycle [1]. Polyamines universally exist in most living organisms including cyanobacteria and human cells, and the best-known polyamines are putrescine, spermidine, and spermine [3]. A few studies have shown that polyamines can induce changes in the structure and function of proteins [5,6,7,8], but how polyamines affect the biological function of protein-protein interaction modules has not been studied. Circadian rhythms are the endogenous oscillations of biological reactions and behaviors in most organisms. On Earth, circadian rhythms have a period of around 24 h, and they play critical roles in regulating cellular functions and gaining evolutionary advantages [9].

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