Speed Dating with KIX: A Single Domain that has Many Partners

IDPs are overrepresented in processes such as signalling and transcription, where proteins often interact with a range of partners. One much-studied key hub protein is the coactivator CBP/p300, whose folded KIX domain binds to a number of different intrinsically disordered transcription factors. The interaction of KIX with several of its ligands has been well studied by equilibrium methods, and structural information is available for many of the complexes. By careful control and consideration of experimental conditions such as temperature and ionic strength we have been able to perform kinetic studies that reveal the mechanism of the association reaction of KIX with cMyb; the fastest protein-protein interaction yet reported. Furthermore, through comparative studies with several binding partners we shed light on an important outstanding question in the IDP field: what is the advantage of disorder to a protein?View Large Image | View Hi-Res Image | Download PowerPoint Slide