Temperature compensation via cooperative stability in protein degradation

TL;DR

This study explores how cooperative stability in protein degradation contributes to temperature compensation in circadian oscillators, revealing nonlinear degradation as a key factor for insensitivity to temperature changes.

Contribution

It demonstrates that nonlinear protein degradation through cooperative stability enhances temperature compensation in circadian clocks, providing a mechanistic understanding.

Findings

Nonlinear degradation improves temperature compensation.

Dimerization influences oscillator period stability.

Cooperative stability is beneficial for circadian robustness.

Abstract

Temperature compensation is a notable property of circadian oscillators that indicates the insensitivity of the oscillator system's period to temperature changes; the underlying mechanism, however, is still unclear. We investigated the influence of protein dimerization and cooperative stability in protein degradation on the temperature compensation ability of two oscillators. Here, cooperative stability means that high-order oligomers are more stable than their monomeric counterparts. The period of an oscillator is affected by the parameters of the dynamic system, which in turn are influenced by temperature. We adopted the Repressilator and the Atkinson oscillator to analyze the temperature sensitivity of their periods. Phase sensitivity analysis was employed to evaluate the period variations of different models induced by perturbations to the parameters. Furthermore, we used experimental data provided by other studies to determine the reasonable range of parameter temperature sensitivity. We then applied the linear programming method to the oscillatory systems to analyze the effects of protein dimerization and cooperative stability on the temperature sensitivity of their periods, which reflects the ability of temperature compensation in circadian rhythms. Our study explains the temperature compensation mechanism for circadian clocks. Compared with the no-dimer mathematical model and linear model for protein degradation, our theoretical results show that the nonlinear protein degradation caused by cooperative stability is more beneficial for realizing temperature compensation of the circadian clock.