pKID Binds to KIX via an Unstructured Transition State with Nonnative Interactions
Liza Dahal1, Tristan O C Kwan1, Sarah L Shammas1
1Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
Biophysical Journal
|December 21, 2017
Summary
Intrinsically disordered proteins like pKID bind partners with few initial interactions. Most folding occurs after binding, a common feature in protein-protein interactions.
Area of Science:
- Molecular Biology
- Biophysics
- Protein Dynamics
Background:
- Intrinsically disordered proteins (IDPs) play key roles in cellular signaling and transcription.
- The CREB protein's disordered pKID region interacts with KIX, regulating cAMP-responsive genes crucial for memory.
- Understanding these interactions is vital for comprehending IDP functions.
Purpose of the Study:
- To experimentally investigate the transition state of the pKID-KIX interaction.
- To determine the role of specific residue mutations on the binding kinetics.
- To elucidate the mechanism of coupled folding and binding in IDPs.
Main Methods:
- Kinetic analysis of pKID mutants (interface and solvent-exposed residues).
- Experimental probing of the transition state during pKID-KIX binding.
- Comparison of experimental findings with computational and existing literature data.
Main Results:
- Minimal specific interactions are needed for the initial pKID-KIX binding event.
- The transition state involves a small number of weak, including non-native, interactions.
- Significant protein folding occurs post-initial binding, not pre-binding.
Conclusions:
- The pKID-KIX interaction mechanism involves transient, weak interactions at the transition state.
- Coupled folding and binding in IDPs may commonly feature post-binding folding.
- Findings align with computational studies and experimental data from other IDP systems.
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