Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session II

39-POS Board 15 Coupled Folding Upon Binding of Transcription Factors and Allostery within the KIX System Sarah Shammas , Jane Clarke. University of Cambridge, Cambridge, United Kingdom. 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 a number of different intrinsically disordered transcription factors at two separate sites on its surface. 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. We have performed comparative stopped-flow experiments to determine the association and dissociation rates for six different disordered ligands, shedding light on the mechanism of these coupled folding and binding reactions. These are shown to be the fastest protein-protein interactions yet reported (without long-range electrostatic attraction). We further describe the general mechanistic basis for the positive allostery between the two binding sites of KIX.

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