Modelling proteome dynamics at the limits of cellular life

Overview & Synopsis

This work investigates the dynamical behaviour of proteomes belonging to three different bacteria, each adapted to a distinct thermal environment.Recent research has focused on understanding the thermal limits of a cell, and the relationship with protein unfolding. It has been suggested that the denaturation of the cytoplasmic proteins under high temperatures determines the upper thermal limit of cellular metabolism. Two pictures have been proposed to explain this connection. Ken Dill and colleagues suggested that the entire proteome undergoes cooperative unfolding at the cell's death temperature. In contrast, Piccotti and coworkers proposed that the unfolding of only a small set of essential proteins is sufficient to arrest metabolism at elevated temperatures. Recent studies combining neutron scattering and molecular simulations have shown that proteome dynamics in mesophilic Escherichia coli strongly indicates cytoplasmic protein unfolding, with a only a small fraction of proteins unfolding at cell death, supporting the latter picture. The link between proteome dynamics and cell death in extremophilic species remains unclear. Advanced computational tools and experimental measurements are crucial for analyzing the complexity of cellular dynamics. In this study, molecular dynamics simulations and neutron scattering were employed to investigate the proteome dynamics of extremophilic bacteria, across different timescales - from sub-nanosecond local motions to nanosecond global translational and rotational motions - while comparing these findings to previous results from the mesophilic organism. The findings reveal that, on the sub-nanosecond scale, protein fluctuations in all bacteria reach a common threshold at their respective cell death points, suggesting that evolutionary adaptations in cytoplasmic viscosity ensure functional protein motion within their thermal niches. On the nanosecond scale, a diffusion slow-down of the proteome aligns with the upper thermal limits for mesophilic and hyperthermophilic bacteria. However, the psychrophilic organism shows a distinct behavior, with its proteome exhibiting remarkable resistance to thermal denaturation. In this case, cell death precedes protein unfolding by about 20 K, a unique anomaly that mirrors the behavior of cold-adapted enzymes, which cease functioning long before their structure is compromised by thermal unfolding.