This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Tiny insects called aphids inject hundreds of mysterious proteins into plants, hijacking the plants' own genomes to build galls: structures made of plant tissue but constructed to the insects' specifications to house and feed their offspring. Now, scientists in the lab of Investigator David Stern, Ph.D., at the Stowers Institute for Medical Research, in collaboration with structural biologists in the lab of Angela Gronenborn at the University of Pittsburgh, have discovered that thousands of these proteins across seven aphid species are built on a shared architectural plan.
Evolution has remodeled that plan so extensively that it may equip aphids with a molecular arsenal for manipulating plants and slipping past their defenses. "We've been very focused on what these proteins are actually doing in the plant," Stern said. "How do these proteins function?
They don't look like anything that we've seen before. One way to try to gain insight into that problem is to solve the 3D structure of these proteins, and that was the motivation for this project." The findings, published Sept. 2, 2026, in the Proceedings of the National Academy of Sciences, demonstrate a new way to use AlphaFold2, an AI system that predicts protein structures, on rapidly evolving proteins that have long resisted study. The approach could help scientists study other such proteins, including those involved in immunity, host-parasite interactions and agriculture.
The findings also open a window into an evolutionary arms race between aphids and the plants they attack. Stern and his team previously discovered this family of molecules and named them BICYCLE proteins after their repeating cysteine motif. From the start, the proteins presented a problem.
Biologists usually investigate what an unknown protein does by comparing its amino acid sequence with the millions already cataloged in public databases; a close match to a known protein is a strong clue. Searches for BICYCLE proteins returned no matches. The proteins are changing so quickly, generation after generation, that their sequences have been rewritten beyond the point where those comparisons can recognize any family resemblance.
"We could tell immediately that they didn't look like any other proteins that you might find in a database," Stern said. That speed is itself a signature of conflict. Proteins at the front line between a parasite and its host tend to evolve fastest because each side is under constant pressure to counter the other's latest move.
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