Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime
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Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime. / Elkjær, Steffie; Due, Amanda D.; Christensen, Lise F.; Theisen, Frederik F.; Staby, Lasse; Kragelund, Birthe B.; Skriver, Karen.
In: Communications Biology , Vol. 6, 63, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime
AU - Elkjær, Steffie
AU - Due, Amanda D.
AU - Christensen, Lise F.
AU - Theisen, Frederik F.
AU - Staby, Lasse
AU - Kragelund, Birthe B.
AU - Skriver, Karen
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-023-04445-6
DO - 10.1038/s42003-023-04445-6
M3 - Journal article
C2 - 36653471
AN - SCOPUS:85146485522
VL - 6
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
M1 - 63
ER -
ID: 334258306