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, Jahrgang 22, Nr. 3, 04.03.2014, S. 466-77.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -