Title
Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime
Author
Steffie Elkjær, Amanda D. Due, Lise F. Christensen, Frederik F. Theisen, Lasse Staby, Birthe B. Kragelund & Karen Skriver
Year
2023
Journal
Communication Biology
Abstract
Transcription depends on complex networks, where folded hub proteins interact with intrinsically disordered transcription factors undergoing coupled folding and binding. For this, local residual structure, a prototypical feature of intrinsic disorder, is key. Here, we dissect the unexplored functional potential of residual structure by comparing structure, kinetics, and thermodynamics within the model system constituted of the DREB2A transcription factor interacting with the αα-hub RCD1-RST. To maintain biological relevance, we developed an orthogonal evolutionary approach for the design of variants with varying amounts of structure. Biophysical analysis revealed a correlation between the amount of residual helical structure and binding affinity, manifested in altered complex lifetime due to changed dissociation rate constants. It also showed a correlation between helical structure in free and bound DREB2A variants. Overall, this study demonstrated how evolution can balance and fine-tune residual structure to regulate complexes in coupled folding and binding, potentially affecting transcription factor competition.
Full Article
Instrument
J-810
Keywords
residual, helix, structure, thermodynamics, DREB2A