Folding of an Intrinsically Disordered Protein Upon Binding to a Target

8 Folding of an Intrinsically Disordered Protein Upon Binding to a Target 

Coupled folding and binding is a frequent theme in the field of intrinsically disordered proteins (see Chap. 6). One of the earliest examples of this phenomenon was the interaction of the phosphorylated kinase-inducible domain (pKID) of the transcription factor CREB with the KIX domain of the transcriptional coactivator CBP. Free pKID is unfolded in solution [21], but folds into an orthogonal pair of helices, aA and aB, upon binding to the folded KIX domain (Fig. 1.5) [23]. We have recently posed the question, what is the 

The encounter complex represents an ensemble in which nonspecific hydrophobic interactions occur at a number of sites. The primary interactions in the encounter complex involve a hydrophobic cluster (Y134, 1137, L138, and L141) in the unfolded aB region of pKID contacting hydrophobic patches on KIX. The encounter complex was invoked to reconcile the behavior of the cross-peaks in the HSQC titrations with the Aw values obtained from the relaxation dispersion measurements a better correlation is observed between the Aoj values and equilibrium chemical shift differences AS which utilize the encounter complex (Fig. 1.7). The structure of the binding intermediate can also be inferred from the chemical shift and relaxation data. The aA helix is nearly fully folded in the intermediate, whereas the aB helix is only partially folded. 

Radhakrishnan, G.C. Perez-Alvarado, H.J. Dyson, P.E. Wright, FEBS Lett. 430, 317-322 (1998) 

Experimental and Simulation Studies of the Folding/Unfolding of Goat a-Lactalbumin 

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