Optimizing the Photocontrol of bZIP Coiled Coils with Azobenzene Crosslinkers: Role of the Crosslinking Site
Abstract
DNA binding by bZIP‐type coiled‐coil proteins can be inhibited by dominant negative versions of the proteins in which the N‐terminal basic region is replaced by an acidic extension. Photocontrol of bZIP function can be achieved by introducing intramolecular azobenzene‐based crosslinkers into dominant negatives. We show that the largest degree of photocontrol is achieved when the crosslinker is introduced into the zipper region of the dominant negative between Cys residues placed at f sites in the heptad segment showing the highest intrinsic helical propensity. The overall affinity of the dominant negative can then be tuned by varying the length of the acidic extension.
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Achieving the desired balance between multiple target coiled-coil states often requires several rounds of trial-and-error and a detailed understanding of the energetic factors that discriminate between alternative topologies and oligomerization states.
“While this has been accomplished in a number of cases,18−31 achieving the desired balance between multiple target coiled-coil states often requires several rounds of trial-and-error and a detailed understanding of the energetic factors that discriminate between alternative topologies and oligomerization states.”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [24]
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- Authors
- Ali, A. M., Forbes, M. W., & Woolley, G. A.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Woolley, G. Andrew
- Venue
- ChemBioChem
- Publisher
- Wiley
- Published
- 2015-06-30
- Volume
- 16
- Issue
- 12
- Pages
- 1757-1763
- ISSN
- 1439-4227 (ISSN-L)
- 1439-7633
- OpenAlex
- W2137583976
- Cited by
- 25
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ChemBioChem (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Photochromic and Fluorescence Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- bZIP transcription factors, coiled-coil proteins, photocontrol, dominant negative effect, DNA binding inhibition, heptad repeat, helical propensity, intramolecular crosslinking, photoisomerization
- MeSH terms
- Amino Acid Sequence, Azo Compounds, Base Sequence, Circular Dichroism, Cross-Linking Reagents, Light, Molecular Sequence Data, Spectrometry, Mass, Electrospray Ionization, CREB-Binding Protein, Basic-Leucine Zipper Transcription Factors
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