A Frustrated Binding Interface for Intrinsically Disordered Proteins [Molecular Biophysics]

January 13th, 2014 by Jemth, P., Mu, X., Engstrom, A., Dogan, J.

Intrinsically disordered proteins are very common in the eukaryotic proteome and many of them are associated with diseases. Disordered proteins usually undergo a coupled binding-and-folding reaction and often interact with many different binding partners. Using double mutant cycles, we mapped the energetic landscape of the binding interface for two interacting disordered domains and found it to be largely suboptimal, in terms of interaction free energies, despite relatively high affinity. These data depict a frustrated energy landscape for interactions involving intrinsically disordered proteins, which is likely a result of their functional promiscuity.