Protein Disorder Flips Switch

The binding of one molecule to a protein can affect subsequent binding of another molecule. That molecular response is known as allostery. Scientists already knew that intrinsic protein disorder—the lack of a defined structure—can modulate allosteric effects such as cooperativity. In positive cooperativity, binding of a molecule at one site increases binding of another molecule at a different site. Negative cooperativity decreases binding of the second molecule. Ashok A. Deniz, Peter E. Wright, and co-workers at Scripps Research Institute, La Jolla, Calif., now show that an intrinsically disordered protein and its binding partners can switch between positive and negative cooperativity (Nature 2013, DOI: 10.1038/­nature12294). The researchers examined systems consisting of truncated versions of the intrinsically disordered protein E1A and two of its binding partners. The E1A constructs offer different sites for complexing with partners. They were tagged with fluorescent agents to monitor E1A folding, which would vary depending on the system’s cooperativity. Over a broad range of concentrations of the two binding partners, the population of various protein complexes changed. They observed changes in the binding cooperativity sign and magnitude, depending on the availability of E1A binding sites. The researchers propose that such effects may be a common control mechanism in protein networks.