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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