pKID Binds to KIX via an Unstructured Transition State with Nonnative Interactions.
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Dahal, L., Kwan, T. O., Shammas, S. L., & Clarke, J. (2017). pKID Binds to KIX via an Unstructured Transition State with Nonnative Interactions.. Biophysical journal, 113 (12), 2713-2722. https://doi.org/10.1016/j.bpj.2017.10.016
Understanding the detailed mechanism of interaction of IDPs with their partners is crucial to comprehend their functions in signalling and transcription. Through its interaction with KIX, the disordered pKID region of CREB protein is central in the transcription of cAMP responsive genes, including those involved in long-term memory. Numerous simulation studies have investigated these interactions. Combined with experimental results, these can provide valuable and comprehensive understanding of the mechanisms involved. Here, we probe the transition state of this interaction experimentally through analysing the kinetic effect of mutating both interface and solvent exposed residues in pKID. We show that very few specific interactions between pKID and KIX are required in the initial binding process. Only a small number of weak interactions are formed at the transition state, including non-native interactions, and most of the folding occurs after the initial binding event. These properties are consistent with computational results and also the majority of experimental studies of IDP coupled folding and binding in other protein systems, suggesting that these may be common features.
Protein Binding, Mutation, Models, Molecular, Cyclic AMP Response Element-Binding Protein, Protein Stability, Intrinsically Disordered Proteins, Protein Domains
MRC Career Development Fellow (award MR/N024168/1)
Wellcome Trust (095195/Z/10/Z)
External DOI: https://doi.org/10.1016/j.bpj.2017.10.016
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276397
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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