Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference

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Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference. / Pogenberg, Vivian; Consani Textor, Larissa; Vanhille, Laurent; Holton, Simon J; Sieweke, Michael H; Wilmanns, Matthias.

In: STRUCTURE, Vol. 22, No. 3, 04.03.2014, p. 466-77.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Pogenberg, V, Consani Textor, L, Vanhille, L, Holton, SJ, Sieweke, MH & Wilmanns, M 2014, 'Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference', STRUCTURE, vol. 22, no. 3, pp. 466-77. https://doi.org/10.1016/j.str.2013.12.017

APA

Pogenberg, V., Consani Textor, L., Vanhille, L., Holton, S. J., Sieweke, M. H., & Wilmanns, M. (2014). Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference. STRUCTURE, 22(3), 466-77. https://doi.org/10.1016/j.str.2013.12.017

Vancouver

Bibtex

@article{5949f694ef96467caaff02e4e5bc7cf8,
title = "Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference",
abstract = "The ability of basic leucine zipper transcription factors for homo- or heterodimerization provides a paradigm for combinatorial control of eukaryotic gene expression. It has been unclear, however, how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements. To unravel the molecular basis of such coupled preferences, we determined two high-resolution structures of the transcription factor MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element. The structures revealed several unexpected and dimer-specific coiled-coil-heptad interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them showed a strong preference for MafB/c-Fos heterodimerization and enabled selection of heterodimer-favoring over homodimer-specific Maf-recognition element variants. Our data provide a concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.",
keywords = "Amino Acid Sequence, Animals, Basic-Leucine Zipper Transcription Factors/chemistry, Binding Sites, DNA/metabolism, MafB Transcription Factor/chemistry, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Engineering/methods, Protein Multimerization, Proto-Oncogene Proteins c-fos/chemistry",
author = "Vivian Pogenberg and {Consani Textor}, Larissa and Laurent Vanhille and Holton, {Simon J} and Sieweke, {Michael H} and Matthias Wilmanns",
note = "Copyright {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",
year = "2014",
month = mar,
day = "4",
doi = "10.1016/j.str.2013.12.017",
language = "English",
volume = "22",
pages = "466--77",
journal = "STRUCTURE",
issn = "0969-2126",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference

AU - Pogenberg, Vivian

AU - Consani Textor, Larissa

AU - Vanhille, Laurent

AU - Holton, Simon J

AU - Sieweke, Michael H

AU - Wilmanns, Matthias

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/3/4

Y1 - 2014/3/4

N2 - The ability of basic leucine zipper transcription factors for homo- or heterodimerization provides a paradigm for combinatorial control of eukaryotic gene expression. It has been unclear, however, how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements. To unravel the molecular basis of such coupled preferences, we determined two high-resolution structures of the transcription factor MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element. The structures revealed several unexpected and dimer-specific coiled-coil-heptad interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them showed a strong preference for MafB/c-Fos heterodimerization and enabled selection of heterodimer-favoring over homodimer-specific Maf-recognition element variants. Our data provide a concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.

AB - The ability of basic leucine zipper transcription factors for homo- or heterodimerization provides a paradigm for combinatorial control of eukaryotic gene expression. It has been unclear, however, how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements. To unravel the molecular basis of such coupled preferences, we determined two high-resolution structures of the transcription factor MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element. The structures revealed several unexpected and dimer-specific coiled-coil-heptad interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them showed a strong preference for MafB/c-Fos heterodimerization and enabled selection of heterodimer-favoring over homodimer-specific Maf-recognition element variants. Our data provide a concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.

KW - Amino Acid Sequence

KW - Animals

KW - Basic-Leucine Zipper Transcription Factors/chemistry

KW - Binding Sites

KW - DNA/metabolism

KW - MafB Transcription Factor/chemistry

KW - Mice

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Mutation

KW - Protein Conformation

KW - Protein Engineering/methods

KW - Protein Multimerization

KW - Proto-Oncogene Proteins c-fos/chemistry

U2 - 10.1016/j.str.2013.12.017

DO - 10.1016/j.str.2013.12.017

M3 - SCORING: Journal article

C2 - 24530283

VL - 22

SP - 466

EP - 477

JO - STRUCTURE

JF - STRUCTURE

SN - 0969-2126

IS - 3

ER -