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DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation
Published on: December 29, 2021
Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor
Jing Li1,2, Jordan T White1, Harry Saavedra1,2
1Department of Biology, Johns Hopkins University, Baltimore, United States.
Elife
|October 13, 2017
Summary
Intrinsically disordered proteins (IDPs) allosterically control function through energetic frustration, not just structure. The human glucocorticoid receptor uses this mechanism, modulated by protein length, to tune cellular signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Protein Science
Background:
- Intrinsically disordered proteins (IDPs) lack stable tertiary structures but are crucial for cellular signaling via allostery.
- Traditional allostery models focus on structural changes in ordered proteins, leaving the mechanism in IDPs unclear.
Purpose of the Study:
- To elucidate the mechanism of allosteric function in intrinsically disordered proteins (IDPs).
- To investigate how IDPs can simultaneously regulate transcriptional activation and repression.
Main Methods:
- Investigated a novel allosteric mechanism based on 'energetic frustration' in IDPs.
- Utilized translational isoforms of the human glucocorticoid receptor (GR) differing in disordered region length.
Main Results:
- Demonstrated that IDPs can allosterically control function by tuning energetic frustration.
- Showed that varying the length of the disordered region in GR isoforms modulates the degree of frustration and signaling output.
- Identified simultaneous tuning of transcriptional activation and repression as a key function regulated by this mechanism.
Conclusions:
- Proposed a frustration-based model for allostery in IDPs, explaining their signaling roles.
- Highlighted the significance of protein length variation in disordered regions for modulating allosteric signaling.
- Suggested this model is broadly applicable to understanding signaling in other IDPs.
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