Budding yeast study brings molecular biology to climate change – sciencedaily


Common yeasts are able to adapt and thrive in response to long-term temperature rise by altering the shape, location and function of some of their proteins. The surprising findings demonstrate the unrecognized plasticity at the molecular and conformational level of proteins and bring the power of molecular biology to the body’s response to climate change. The results of the Zhou laboratory of the Buck Institute in collaboration with the Si laboratory of the Stowers Institute are published in Molecular cell.

Temperature is an unstable parameter in nature, affecting almost all aspects of life by altering the stability of proteins and the rate of metabolism. Buck Institute Fellow Chuankai “Kai” Zhou, PhD, lead scientist on the study, says previous research provides in-depth knowledge of how acute and short-term increases in temperature misfold proteins, revealing how cells respond to such challenges by upregulating molecular chaperones and other stresses. response proteins to refold / break down these misfolded proteins to help unprepared cells survive sudden changes in their environment. However, Zhou says it’s largely unknown whether cells will continue this cycle of improper folding-folding / degrading of proteins when increasing temperature becomes a long-term challenge.

“This is a critical issue as climate change and global warming are causing a rise in temperature that will span generations for most of the species currently living on earth,” he said. “Understanding how and if organisms are prepared for such long-term global warming at the molecular level is essential for us to be able to address the future of our ecosystem. “

In this study, Buck researchers tracked and compared yeast grown at room temperature to cells grown at 95 degrees Fahrenheit (35 degrees Celsius) for over 15 generations. The higher temperature initially resulted in the well-documented stress response seen with short-term temperature rise (or heat shock), including protein aggregation and increased expression of protective chaperones. After the yeast grew at a high temperature for a few generations, the researchers saw the cells recover and their growth rate gradually accelerated. After 15 generations, protein aggregates have disappeared and many acute stress regulators have returned to baseline expression levels. Whole genome sequencing did not find any genetic mutations. Zhou somehow says that the yeast has adapted to the temperature challenge.

Using impartial imaging screening and machine-learning-based image analysis, scientists analyzed millions of cells for the entire yeast proteome and found hundreds of proteins that altered their expression patterns, including abundance and subcellular locations, after cells had adapted to the higher temperatures. “Interestingly, proteins that tend to be misfolded by acute stress reduced their expression after the yeast acclimatized to the new environment,” Zhou said. “This suggests that a possible strategy to avoid the erroneous folding / refolding cycle under a persistent temperature challenge would involve reducing the load of heat labile proteins.” Zhou says subcellular localization is a determinant of protein function. Proteins alter their subcellular distribution under persistent temperature change either to protect themselves from thermal instability or to perform new functions in compensation for the reduction of other heat labile proteins, or both.

“The most exciting and unexpected changes are happening at the sub-molecular level of proteins,” Zhou said. “Once the yeast ‘realized’ that heat stress was long term, it changed a lot. Some of their proteins changed conformation (shape). The current paradigm of gene-protein function research has been built on the belief that a protein has ONE final structure. We show that this is not the case, at least for some of the proteins that responded to the change in temperature. “

This discovery comes from a new proteomic-structural screening pipeline developed by Zhou and his colleagues that allowed them to identify many proteins that took on an alternate shape or conformation after the yeast acclimatized to its new environment. . Importantly, these changes in protein conformation were not caused by genetic mutations, and most of them also did not result in post-translational modifications. Using Fet3p, a copper-containing glycoprotein, as an example, the researchers found that the protein changed locations over generations, moving from the endoplasmic reticulum to the cell membrane during thermal acclimatization. “What’s most amazing is that the conformation of proteins is also different. It also changes its interacting proteins,” Zhou said.

By verifying protein-protein interactions and associated molecular functions, the researchers found that Fet3p, produced at different temperatures, has distinct functions in different cell compartments. Zhou says thermal acclimatization altered protein folding and function, allowing a polypeptide to take on multiple structures and functions in moonlight depending on the growing environment. “These results together show the plasticity of the proteome and reveal prior unknown strategies available to organisms facing long-term temperature challenges. For a simple organism like yeast, which has very limited alternative splicing, such plasticity of the proteome or alternative protein folding induced by the environment conditions, allows this organism to survive a surprisingly wide range of difficult habitats. “

While excited about the discovery of an evolutionary coded strategy that allows yeast to adapt to different temperatures, Zhou points out that resilience cannot be assumed. “We know there is a limit to plasticity – above a certain temperature the yeast will die. Our hope is that this work will enable efforts to learn from Mother Nature about how organisms grow. adapt to climate change by implementing the encoded plasticity of their proteins.Some species have undergone several rounds of climate change over the course of Earth’s history and their genomes / proteomes may have learned to cope with such changes. at the same time, many species are new to climate change and are most likely threatened with extinction due to current global warming. We are happy to contribute to pressing issues at the molecular level and welcome collaborations. “

Zhou will continue to dig into the molecular details of what changes inside cells during long-term temperature changes and plans to include single animals in his exploration of protein plasticity. He will also study the impact of temperature change on aging.

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