Coupling of binding and differential subdomain folding of the intrinsically disordered transcription factor CREB. Issue 7 (19th December 2022)

• Record Type: Journal Article
• Authors: Bentley, Emily P.; Scholl, Daniel; Wright, Peter E.; Deniz, Ashok A.
• Is Part Of: FEBS letters. Volume 597:Issue 7(2023)
• Page Start: 917
• Page End: 932
• Publication Date: 2022-12-19
• Subjects: bZIP -- dimerization -- folding upon binding -- intrinsically disordered protein -- single‐molecule FRET -- transcription factor; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14554
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The cyclic AMP response element binding protein (CREB) contains a basic leucine zipper motif (bZIP) that forms a coiled coil structure upon dimerization and specific DNA binding. Although this state is well characterized, key features of CREB bZIP binding and folding are not well understood. We used single‐molecule Förster resonance energy transfer (smFRET) to probe conformations of CREB bZIP subdomains. We found differential folding of the basic region and leucine zipper in response to different binding partners; a strong and previously unreported DNA‐independent dimerization affinity; folding upon binding to nonspecific DNA; and evidence of long‐range interdomain interactions in full‐length CREB that modulate DNA binding. These studies provide new insights into DNA binding and dimerization and have implications for CREB function. Abstract : In the basic leucine zipper (bZIP) domain of the disordered cyclic AMP response element binding protein (CREB), we show that the leucine zipper folds upon DNA‐independent dimerization, whereas the basic region requires DNA for folding. We measure affinities for bZIP dimerization and binding of specific and nonspecific DNA and show that, in full‐length CREB, DNA binding competes with intramolecular interactions.