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Intrinsically disordered proteins: A conversation with Rohit Pappu
Date:9/20/2012

d proteins take part in catalysis and transport. Intrinsically disordered proteins are important for signaling and regulation.

Why are disordered proteins involved in signaling and regulation?

I think there are two logical reasons. One is that complexes involving intrinsically disordered proteins are short-lived and the other is that they typically bind many rather than just one molecule.

If a molecule cannot fold except in the context of a complex, then some of the energy used for folding must come from intermolecular interactions. And if the molecule has taken out an energy loan, the complex that forms is not going to be very stable or long-lived.

You're combining high specificity (because the protein will only fold when it recognizes the molecule with which it forms a complex) with low overall affinity (because the complex is not very stable).

The many-to-one interactions arise because disordered proteins typically function through short amino acid stretches instead of large protein-protein interfaces. So a single polypeptide stretch can interact with multiple targets. One motif talks to one protein, and a second motif talks to another protein, but through the chain they can communicate with each other.

That's why these molecules happen to be at hubs within networks. They're trafficking information through networks like the air traffic control tower in an airport hub. Because most of their functions are carried out by these very short motifs, they are capable of coordinating large amounts of information that are disparate in nature. You get many things happening at the same time.

What was remarkable to me about your perspective is that you emphasized functionality of these proteins. Isn't the name a bit misleading?

You're right. As we get to know them better we've thought we should have called disordered proteins, molecular rheostats. But to a physicist disorder just means t
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Contact: Diana Lutz
dlutz@wustl.edu
314-935-5272
Washington University in St. Louis
Source:Eurekalert

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