What is it about?
Proteins are the molecular machines of life and their ability to work depends entirely on their shape. For decades, scientists believed that a specific group of proteins, known as "solenoids" - which look like simple, coiled springs - were never knotted. However, an international team led by Prof. Joanna Sulkowska at the University of Warsaw has discovered a groundbreaking new family: The Knotted Solenoids. Instead of a simple coil, these proteins perform a complex "skip-and-backtrack" maneuver as they form, essentially tying themselves into a physical knot (similar to a three-loop trefoil knot). To prove this wasn't just a computer error, the researchers used X-ray to map the exact position of every atom. For a long time, these structures were just a "theoretical guess" made by AI like AlphaFold; now, we have the experimental "photograph" proving the AI was right.
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Why is it important?
This discovery is a major milestone for the field of "Digital Biology." To understand why nature would evolve such a complex, knotted shape, our team put these proteins through rigorous stress tests, exposing them to high heat and harsh chemicals. We found that these structures are incredibly tough - much more resilient than standard proteins. Using advanced computer simulations, we "virtually" pulled the protein apart to watch how the knot disappears during unfolding. We discovered that these knots have been "evolutionarily locked" in place for millions of years across different species of bacteria. This tells us the knot isn't a biological accident. Instead, it acts like a structural anchor, providing the protein with the extraordinary durability it needs to survive. Understanding these "nature-made" knots allows us to design better, more stable molecules for future technology and medicine.
Perspectives
Revealing the knotted nature of these proteins opens a new frontier in medicine. Solenoid proteins are frequently linked to bacterial infections and neurodegenerative diseases. By understanding exactly how these knots are tied and stabilized, scientists can now design smarter therapies that target these structures with surgical precision. This work moves us closer to a world where we can not only map the protein universe but also manipulate its complex geometry to treat diseases that were once considered unreachable.
Julia Sikorska
University of Warsaw
Read the Original
This page is a summary of: Novel Knotted Solenoid fold with order-shifted coil arrangement leads to nontrivial 3
1
topology, Proceedings of the National Academy of Sciences, April 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2525920123.
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