Stereochemistry in the disorder-order continuum of protein interactions.

Intrinsically disordered proteins can bind via the formation of highly disordered protein complexes without the formation of three-dimensional structure. Most naturally occurring proteins are levorotatory (L)-that is, made up only of L-amino acids-imprinting molecular structure and communication with stereochemistry. By contrast, their mirror-image dextrorotatory (D)-amino acids are rare in nature.

Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime.

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.

Flanking Disorder of the Folded αα-Hub Domain from Radical Induced Cell Death1 Affects Transcription Factor Binding by Ensemble Redistribution.

Protein intrinsic disorder is essential for organization of transcription regulatory interactomes. In these interactomes, the majority of transcription factors as well as their interaction partners have co-existing order and disorder. Yet, little attention has been paid to their interplay.