Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants

Frederik Friis Theisen, Andreas Prestel, Steffie Elkjær, Yannick H. A. Leurs, Nicholas Morffy, Lucia C. Strader, Charlotte O’Shea, Kaare Teilum, Birthe B. Kragelund () and Karen Skriver ()
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Frederik Friis Theisen: University of Copenhagen
Andreas Prestel: University of Copenhagen
Steffie Elkjær: University of Copenhagen
Yannick H. A. Leurs: University of Copenhagen
Nicholas Morffy: Duke University
Lucia C. Strader: Duke University
Charlotte O’Shea: University of Copenhagen
Kaare Teilum: University of Copenhagen
Birthe B. Kragelund: University of Copenhagen
Karen Skriver: University of Copenhagen

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract The Arabidopsis thaliana DREB2A transcription factor interacts with the negative regulator RCD1 and the ACID domain of subunit 25 of the transcriptional co-regulator mediator (Med25) to integrate stress signals for gene expression, with elusive molecular interplay. Using biophysical and structural analyses together with high-throughput screening, we reveal a bivalent binding switch in DREB2A containing an ACID-binding motif (ABS) and the known RCD1-binding motif (RIM). The RIM is lacking in a stress-induced DREB2A splice variant with retained transcriptional activity. ABS and RIM bind to separate sites on Med25-ACID, and NMR analyses show a structurally heterogeneous complex deriving from a DREB2A-ABS proline residue populating cis- and trans-isomers with remote impact on the RIM. The cis-isomer stabilizes an α-helix, while the trans-isomer may introduce energetic frustration facilitating rapid exchange between activators and repressors. Thus, DREB2A uses a post-transcriptionally and post-translationally modulated switch for transcriptional regulation.

Date: 2024
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DOI: 10.1038/s41467-024-44859-2

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