"Every time you talk to people in the back alleys of protein science," he said, "they tell you their proteins are very flexible or highly dynamic, and this dynamism is important for function."
So Keith did two things. He synthesized all of the information then known about these flexible, highly disordered proteins. And, together with his colleague Vladimir Uversky, he asked if it was possible to predict which sequences would be incapable of folding autonomously. With the help of computer scientists who taught him how to look for patterns in high-dimensional spaces, he learned that 11 out of the 20 amino acids predispose sequences toward being disordered. Today there are about 20 predictors of disorder.
So when I heard this story I thought, "OK, either this is absolutely crackers or it is going to be transformative. I'm going to take a bet on transformative because I find what he's saying compelling."
So during my first two years at Washington University I started to devour the literature. I think I scared a lot of people here who weren't sure they had hired the person they thought they were hiring.
What percentage of proteins are intrinsically disordered?
It goes by kingdoms. So in bacteria and prokaryotic organisms these numbers are pretty small. They're about 5 percent of the proteome, the entire set of proteins made by an organism. But if you go to eukaryotes or multicellular organisms then the numbers get to 30 or 40 percent of the entire proteome.
But if you ask what percentage of sequences that make up the signaling proteome proteins that are busy passing messages to other proteins are intrinsically disordered, then the numbers jump up to 60 to 70 percent.
There seems to be a division of responsibilities. Structure
|Contact: Diana Lutz|
Washington University in St. Louis