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The X-ray Structure of the GCN4-bZIP Bound to ATF/CREB Site DNA Shows the Complex Depends on DNA Flexibility
Abstract
The X-ray structure of the DNA binding domain of the yeast transcriptional activator protein GCN4 bound to a DNA fragment containing the sequence of the perfectly symmetrical ATF/CREB site has been solved to 3.0 A resolution. The architecture of this specific recognition complex supports the current model for bZIP proteins: a homodimer of parallel alpha-helices form an interhelix coiled-coil region via the leucine zipper, and the two N-terminal basic regions fit into the major groove of half sites on opposite sides of the DNA double helix. The structure shows that DNA flexibility plays the predominant role in the preservation of protein contacts with the symmetric ATF/CREB site (ATGACGTCAT) as compared to the pseudo-symmetric AP-1 target site (ATGACTCAT), overcoming the positional displacement of functional groups introduced by the additional G.C base-pair at the center of the ATF/CREB sequence.
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“In the crystal structures of GCN4 homodimers and Jun-Fos heterodimers, g-e' intersubunit salt bridges are visible between oppositely charged amino acids in the gi and e/+5 positions (O'Shea et al., 1991; Ellenberger et al., 1992; Konig & Richmond, 1993; Glover & Harrison, 1995).”
From Oligomerization properties of GCN4 leucine zipper e and g position mutants (1997) · cites this paper as Konig & Richmond, 1993
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Items 201–216 of 216
Production of recombinant human tektin 1, 2, and 4 and in vitro assembly of human tektin 1
Budamagunta, M. S., Guo, F., Sun, N., Shibata, B., FitzGerald, P. G., Voss, J. C., & Hess, J. F. (2017) · Cytoskeleton · doi:10.1002/cm.21418 · Cited by 1
“Short coiled-coil domains within globular proteins, often mediating dimerization, have been solved by crystallization (Ellenberger, Brandl, Struhl, & Harrison, 1992; Konig & Richmond, 1993; O’Shea, Klemm, Kim & Alber, 1991; Saudek et al., 1991).”
MethodPreliminary X-ray diffraction studies of the transcriptional inhibitory antibody Fab41.4.
Mazlo, J., Stanfield, R., Wilson, I. A., Hinrichs, S. H., & Stezowski, J. J. (2001) · Acta Crystallographica Section D: Biological Crystallography · doi:10.1107/s0907444901001135 · Cited by 1
“X-ray diffraction studies have been reported for the prototypic bZIP yeast transcription factor GCN4 bound to AP-1 (O'Shea et al., 1991) and CRE DNA (Ellenberger et al., 1992; Konig & Richmond, 1993).”
BackgroundPeptide models of bZIP proteins: Quantitative analysis of DNA affinity and specificity
Metallo, S., & Schepartz, A. (1995) · Techniques in protein chemistry · doi:10.1016/s1080-8914(06)80047-5 · Cited by 1
Activating Transcription Factor 3 in Pain: A Molecular Regulator and Emerging Biomarker
García‐Domínguez, M. (2026) · Genes · doi:10.3390/genes17091034
“Structural studies have demonstrated that the α -helices of the basic region insert into the major groove of DNA, allowing sequence-specific recognition through hydrogen bonding and hydrophobic interactions with nucleotide bases [57,58].”
A transcription factor-based capture strategy for LAMP detection of wheat stripe mosaic virus.
Andrade, A. V., de Jesus, B. A. P., Fernandes, L., da Silva, F. N., Magalhães, M. D. L. B., & da Silva, G. D. (2026) · Journal of Virological Methods · doi:10.1016/j.jviromet.2026.115388
Fourier Helicity Spectra as Quantifiers of Multiscale ChiralityPreprint
Im, S. W., Ma, J., Moudgal, N., & Kotov, N. A. (2025) · bioRxiv · doi:10.64898/2025.12.15.694500
“( 38 , 39 ) When the right-handed pitch of 33 Å that corresponds to the dominant helical mode of DNA ( Fig.”
Effect of Flanking Bases on the DNA Specificity of EmBP-1
Jong, A. T. D. (2013) · doi:10.1021/bi301404h
CD studies of interaction of a bZIP oligopeptide model with DNA
Votavová, H., Točík, Z., & Šponar, J. (1999) · doi:10.1016/s0022-2860(98)00826-6
Saha, A. (2018) · Springer theses · doi:10.1007/978-981-10-8746-2_1
EVALUATING IN VITRO AND IN VIVO LOOPING EFFICIENCIES OF ARTIFICIAL DNA-BINDING PROTEINS
Sucayan, S. (2014) · doi:10.13016/m2903k
“The GCN4 LZIP protein has been previously shown to bind with high affin- ity to the palindromic CREB site (Hill, Hope, Macke, & Struhl, 1986; König & Richmond, 1993).”
BackgroundStructural characterization of general transcription factor complexes
Bleichenbacher, M. (2002) · doi:10.3929/ethz-a-004471244
Wang, H., Zhou, B., Luo, Y., Miao, Z.-W., Chen, C., Xu, X.-J., & Tang, Y.-Q. (2002) · doi:10.1007/0-306-46859-x_75
Chapter 5 Protein-nucleic acid recognition and interactions
Vrielink, A., & Freemont, P. S. (1996) · Principles of medical biology · doi:10.1016/s1569-2582(96)80109-7
Site-specific reversible conjugation: A novel concept in peptide-DNA interactions
Stanojević, D., & Verdine, G. (1996) · doi:10.1016/s1080-8914(96)80013-5
Mechanistic Studies on the Formation of BZIP•DNA Interfaces
Paolella, D. N., Palmer, C., Metallo, S., & Schepartz, A. (1995) · doi:10.1007/978-94-011-0353-4_11
“DNA [8,9].”
BackgroundInfluential
Metadata
- Authors
- König, P., & Richmond, T. J.
- Affiliations
- ETH Zurich (CH)
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1993-09
- Volume
- 233
- Issue
- 1
- Pages
- 139-154
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2056115277
- Cited by
- 287
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 8
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- GCN4, bZIP transcription factors, DNA-binding domain, DNA flexibility, protein-DNA complex structure, leucine zipper, coiled coil, AP-1 binding site, major groove binding
- MeSH terms
- Amino Acid Sequence, Base Sequence, Binding Sites, Blood Proteins, Crystallization, DNA-Binding Proteins, Fungal Proteins, Genes, Synthetic, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Peptide Fragments, Plant Proteins, Protein Conformation, Protein Kinases, Recombinant Proteins, Regulatory Sequences, Nucleic Acid, Transcription Factors, X-Ray Diffraction, Leucine Zippers, Cyclic AMP Response Element-Binding Protein, Protein Structure, Secondary, Saccharomyces cerevisiae Proteins, Macromolecular Substances, Basic-Leucine Zipper Transcription Factors, Activating Transcription Factors, G-Box Binding Factors
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