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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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