Brittany Trang , 2025-07-17 18:00:00
For decades, structural biologists shoved what looked like shoddy data in the back of their closets, embarrassed. While attempting to gather the structures of proteins, they would sometimes find that all or at least a portion of the protein would just not show up correctly in the data.
Joel Sussman, a former head of the Protein Data Bank, remembers when he found his first intrinsically disordered protein, though it wasn’t called that at the time. He showed it to a collaborator. “‘Oh, Joel, you’re not a very good biochemist. Obviously, it has a structure and you’re confused,’” he recalled her saying.
Most proteins fold into shapes with distinct elements: the ordered spiral of an alpha-helix, like a piece of cavatappi pasta; or beta sheets, like a slice of a lasagna — squiggly lines of pasta amino acids held parallel to each other with cheesy and saucy hydrogen bonds. A central tenet of structural biology is that a protein’s structure dictates its function. But around the same time that the world was preparing for Y2K, structural biologists finally began admitting that — just as Sussman and other scientists had seen — not all proteins have a permanent shape. A surprisingly large amount of important proteins (in fact, over half of all proteins in eukaryotes, it’s estimated) have strands of wiggly “spaghetti” in them.
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