Unforeseen Proteomic Flexibility In Answer To Uniform Temperature Rise Adapted To The Temperature Challenge.

The study of budding yeasts brings molecular biology to climate change.

Temperature is a varying parameter in the wild that affects almost all aspects of life, altering protein stability and metabolic rate. C

huankai "Kai" Zhou, a researcher at the Buck Institute and lead investigator on the study, said previous research provided comprehensive insight into how much short-term temperature increases disrupt proteins and how cells respond to the challenge by creating molecular chaperones and other stressors. 

Proteins respond to the refolding/unfolding of these misfolded proteins to help unprepared cells survive sudden changes in their environment. However, Zhou said it is largely unknown whether cells will continue this cycle of inappropriate protein folding/folding/degradation when rising temperatures become a long-term challenge.

"This is a critical issue because climate change and global warming are causing temperature rises that will last generations for most of the species currently on Earth," he said. "Understanding how and if organisms are prepared at the molecular level for such long-term global warming is critical to addressing the future of our ecosystems."

In this study, Buck researchers tracked and compared yeast grown in a room with cells grown at 35 degrees Celsius for more than 15 generations. Higher temperatures initially cause a well-documented stress response, which is observed with short-term temperature increases (or heat shock), including protein aggregation and increased expression of protective chaperones.

After the yeast had grown at high temperatures for generations, the researchers saw the cells recover and gradually accelerate their growth rate. After 15 generations, protein aggregates disappear, and many acute stress regulators return to their original expression levels. The entire genome sequence does not recognize any genetic mutations. Zhou said the yeast had somehow adapted to the temperature challenge.

Using accurate image filtering and machine-assisted image analysis, the researchers analyzed millions of cells for the entire yeast proteome. They found hundreds of proteins that change their expression patterns, including subcellular frequency and localization, as cells adapt to higher temperatures. "Interestingly, proteins that tend to vibrate inappropriately under acute stress reduce their expression once the yeast adapts to the new environment," Zhou said. 

"This suggests that one possible strategy to avoid improper folding/folding cycles under constant temperature loads would include reducing exposure to thermolabile proteins," Zhou said that subcellular localization is essential for protein function. Proteins change their subcellular distribution with constant temperature changes to protect against thermal instability or to perform new positions, to compensate for the reduction of other thermolabile proteins, or both.

"The most interesting and unexpected changes occurred at the submolecular protein level," Zhou said. "When yeasts realize that heat stress is long term, they change a lot. Some of their proteins change conformation. Paradigm.

This discovery stems from a new proteomic structure screening pipeline developed by Zhou and colleagues that allowed them to identify many proteins that have adopted alternative shapes or conformations after the yeast has adapted to its new environment. Genetic mutations mustn't cause these conformational changes of proteins, and most of them do not result in post-translational modifications.

 Using the example of Fet3p, a multi-copper glycoprotein, the researchers found that the protein changes its location from generation to generation and moves from the endoplasmic reticulum to the cell membrane during thermal acclimatization. "The most amazing thing is that the confirmation of the protein is also different. It also changes the interacting proteins," Zhou said.