Duke researchers recently discovered new applications of a property in proteins that could help organisms endure climate change.
The study was conducted in the Gladfelter Lab in the Duke School of Medicine and published in Current Biology on July 31. The experiment takes advantage of the structural flexibility of intrinsically disordered proteins, explaining a possible mechanism of resilience to disease and climate-change-induced temperature change.
Led by Professor of Cell Biology Amy Gladfelter, the experiment focused on IDPs of the Whi3 protein in the fungus Ashbya gossypii. Unlike traditional proteins that require a specific shape to function, IDPs — which are found in all organisms — are flexible and lack a fixed structure.
"These spaghetti[-like] sequences that are totally disordered can evolve much faster,” Gladfelter said. That way, IDPs are not as constrained as sequences encoding conventional proteins “that [have] to have a particular shape or fold.”
If a protein has a particular shape it must conform to, mutations can cause it to break, she explained. In the disordered tracks, however, there are a number of mutations “flopping around” as the protein does not bind as tightly.
“The cell can acquire mutations in those more quickly, and they don’t get filtered out by selection,” Gladfelter said. As the temperature changes, the mutations become advantageous and there is “more tolerance for variation” because they do not need to take on a particular shape.
Because IDPs are like “wet spaghetti,” they can engage in a “new organizing principle in cell biology” in which proteins and RNAs condense “like dew on a blade of grass.”
The study revealed how the properties of Whi3-based biomolecular condensates can be tuned by changes in temperature. By swapping Whi3 sequences between different fungal strains, the team established a direct link between Whi3 IDP sequence variation and the fungus's ability to handle temperature changes.
According to Gladfelter, the Whi3 protein first caught the researchers’ attention because of a special “polyglutamine” track that it shared with certain human diseases, like Huntington’s.
“We can potentially imagine a future where you prevent the onset of Huntington's disease by shrinking the polyglutamine track in Huntington’s, for example,” she said. “Because there, the length of the track is very much predictive of the disease.”
Insights into these biomolecular condensates in Ashbya gossypii offer potential for enhancing resilience across various organisms. By taking advantage of these mechanisms, scientists may be able to engineer crops with improved tolerance to environmental stresses such as drought and heat, Gladfelter noted. This, in turn, could create more robust agricultural systems and strengthen food security amid a changing climate.
The findings illustrate the potential for new challenges in the future, such as a fungus adapting to the human body and becoming an emerging pathogen. According to Gladfelter, there is a team at Duke working on ways to predict these challenges.
“Could we predict, potentially, the emergence of fungal pathogens that might be arising because of a change in climate that are selecting for organisms that can live in weird environments?” Gladfelter posed. “Because the human body is a weird environment for many organisms.”
Looking to the future, Gladfelter hopes to expand the research to look at new forms of fungi and IDPs to see “how generalizable” the study’s findings can be.
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