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

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Item Type:	Article
Title:	Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference
Creators Name:	Pogenberg, V., Consani Textor, L., Vanhille, L., Holton, S.J., 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
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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