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

Item Type:Article
Title:Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference
Creators Name:Pogenberg, V. and Consani Textor, L. and Vanhille, L. and Holton, S.J. and Sieweke, M.H. and Wilmanns, M.
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, Basic-Leucine Zipper Transcription Factors, Binding Sites, DNA, MafB Transcription Factor, Molecular Models, Molecular Sequence Data, Mutation, Protein Conformation, Protein Engineering, Protein Multimerization, Proto-Oncogene Proteins c-fos, Animals, Mice
Source:Structure
ISSN:0969-2126
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:22
Number:3
Page Range:466-477
Date:4 March 2014
Official Publication:https://doi.org/10.1016/j.str.2013.12.017
PubMed:View item in PubMed

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