Design of a bZip Transcription Factor with Homo/Heterodimer-Induced DNA-Binding Preference

Pogenberg, Vivian; Consani Textor, Larissa; Sieweke, Michael H.; Wilmanns, Matthias; Holton, Simon J.; Vanhille, Laurent

doi:10.1016/j.str.2013.12.017

Journal Article

PUBDB-2015-01355

Design of a bZip Transcription Factor with Homo/Heterodimer-Induced DNA-Binding Preference

Pogenberg, V. (Corresponding Author)>Extern*EMBL* ; Consani Textor, L. ; Vanhille, L. ; Holton, S. ; Sieweke, M. ; Wilmanns, M.>Extern*EMBL*

2014
Elsevier Science London [u.a.]

Structure 22(3), 466 - 477 (2014) [10.1016/j.str.2013.12.017]

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Please use a persistent id in citations: doi:10.1016/j.str.2013.12.017

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.

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