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

hermal fluctuations are dominant, so for physicists it's an accurate description. The problem is that in the biomedical field the word disorder has been coopted for disease.

You mention several tricks these proteins have up their sleeves. One I thought was clever was modulating the local chemical environment to encourage a particular reaction.

This is a very important idea. If you're doing chemistry in a test tube, and you want to make a reaction go, you increase the concentration of the reactants: A needs to bump into B and do so often. But this is a matter of probability so you might need a gazillion molecules of A and bazillion of B to get some statistics.

But if there's a tether between A and B, they're guaranteed to bump into each other quite often. You might be able to get away with a handful of molecules instead of gazillion.

The loose tether, in effect, increases the concentration of A around B, and the tether is often a disordered region.

Another thing you mentioned was cryptic disorder: the idea that structured proteins can become disordered. That's such a backward flip.

Richard Kriwacki of St. Jude Children's Research Hospital, a co-author of this perspective, is the person who made the clearest discovery in that regard. He shows that two structured domains can come together this is part of the whole p53 tumor suppressor apparatus and in trying to commingle, they undergo an unfolding transition that exposes sites that otherwise were buried.

This is the idea of cryptic disorder: that domains, by promoting disorder in one another, reveal hidden, or cryptic, motifs or sites that now are available for function.

You mention that in the biomedical community disorder is associated with disease. Your co-author M. Madan Babu of the MRC Laboratory of Molecular Biology in Cambridge has written about this connection.

Yes. Cells make many decisions. They decide
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Contact: Diana Lutz
dlutz@wustl.edu
314-935-5272
Washington University in St. Louis
Source:Eurekalert

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