Proteome plasticity at high temperatures!

Esha Mukherjee, Amity University Noida

By changing the form, location, and function of several of their proteins, common yeast can adapt and survive in response to a long-term change in temperature. The startling findings highlight protein plasticity at the molecular and conformational levels. It demonstrates the ability of molecular biology in understanding organismal responses to climate change. The results of a partnership between the Buck Institute’s Zhou lab and the Stowers Institute’s Si lab have been published in Molecular Cell.

In the wild, temperature is a variable factor that affects practically every element of life by altering proteome stability and metabolism speed. Previous research has revealed how acute, short-term temperature increases misfold proteins. It also showed how cells respond to such challenges by upregulating molecular chaperones and other stress response proteins to refold/degrade misfolded proteins to help unprepared cells survive, according to Buck Institute Fellow Chuankai “Kai” Zhou, Ph.D., lead scientist of the study.

To him, this is an important subject since climate change and global warming will result in a temperature increase that will affect most species currently living on the planet for years. Therefore, understanding how and whether species are equipped at the molecular level for such long-term global warming is crucial to address the future of the environment.

The study:

Buck’s scientists investigated and compared yeast grown at room temperature versus yeast grown at 95 degrees Fahrenheit for more than 15 generations (35 degrees Celsius). The greater temperature triggered the well-known stress response associated with short-term temperature increases (or heat shock), which included protein aggregation and increased production of protective chaperones. Researchers noticed that after a few generations of high-temperature growth, the yeast cells recovered, and their growth rate began to accelerate. Protein clumps vanished after 15 generations, and several acute stress regulators recovered to baseline expression levels. There were no genetic alterations discovered after a whole-genome sequencing. The yeast adapted to the temperature challenge in some way.

Findings of the study:

Scientists analyzed millions of cells for the entire yeast proteome using unbiased imaging screening and machine-learning-based image analysis. They discovered hundreds of proteins that changed their expression patterns, including abundance. They even changed when the cells had adapted to the higher temperatures, subcellular localizations. Zhou added, “Interestingly when the yeast adjusted to the new environment, the proteins that are prone to misfolding by acute stress lowered their expression,”.

This suggests that lowering the burden of thermolabile proteins could be one way to avoid the misfolding/refolding cycle in the face of sustained temperature stress.” Subcellular localization, according to Zhou, is a determinant of protein function. Under prolonged temperature changes, proteins modify their subcellular distribution to either protect themselves against thermal instability or to perform new tasks as compensation for the loss of other thermolabile proteins, or both.

“Once the yeasts realize that the heat stress was long-term, they altered a lot,” Zhou said, “the most intriguing and unexpected alterations happen at the submolecular level of the proteins.” The configuration of several of their proteins shifted (shape). The existing gene-protein function paradigm is based on the assumption that a protein has just ONE final configuration. For at least some of the proteins that responded to the temperature shift, we show that this isn’t the case.”

Discussion:

This discovery was made possible by Zhou and colleagues’ development of a novel proteomics-structural screening process, which allowed them to identify several proteins that changed shape or conformation after the yeast adjusted to their new environment. Importantly, these conformational alterations were not induced by genetic mutations, and the majority of them did not result in post-translational modifications. The researchers discovered that during heat acclimation, Fet3p, a multicopper-containing glycoprotein, changed position throughout generations, traveling from the endoplasmic reticulum to the cell membrane. 

The researchers discovered that Fet3p, synthesized at different temperatures, has varied activities in different cellular compartments by evaluating protein-protein interactions and associated molecular functions. Protein folding and function were altered by thermal acclimation, allowing a single polypeptide to take on different forms and moonlight roles depending on the growth environment. These results together show the plasticity of the proteome and reveal previously unknown strategies available to organisms facing long-term temperature challenges.

While Zhou is pleased to have discovered an evolutionary-encoded strategy for yeast to adjust to various temperatures, he cautions that resilience cannot be expected.

CONCLUSION:

The goal of this research helped to learn from Mother Nature about how organisms adapt to climate change by using their proteins’ encoded plasticity. Some species have seen multiple cycles of climate change over Earth’s history, and their genomes/proteomes may have evolved to adapt. At the same time, many species are unaccustomed to climate change and are likely to perish as a result of present global warming. 

FUTURE PERSPECTIVES:

Zhou aims to continue delving into the molecular details of what happens inside cells during long-term temperature changes, and he intends to include simple animals in his protein plasticity research. He’ll also look into the effects of climate change on aging. 

Also read: CRISPR-Cas9 for disease resistance in salmon

References:

1. Domnauer, M., Zheng, F., Li, L., Zhang, Y., Chang, C. E., Unruh, J. R., Conkright-Fincham, J., McCroskey, S., Florens, L., Zhang, Y., Seidel, C., Fong, B., Schilling, B., Sharma, R., Ramanathan, A., Si, K., & Zhou, C. (2021). Proteome plasticity in response to persistent environmental change. Molecular Cell, S1097276521005086. https://doi.org/10.1016/j.molcel.2021.06.028

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