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

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• 作者：Vivian Pogenberg¹ ; ⁶ ; Larissa Consani Textor¹ ; ⁶ ; Laurent Vanhille² ; ³ ; ⁴ ; ⁶ ; Simon J. Holton¹ ; ⁷ ; Michael H. Sieweke² ; ³ ; ⁴ ; ⁵ ; Matthias Wilmanns¹ ; ^{wilmanns@embl-hamburg.de" class="auth_mail}
• 刊名：Structure
• 出版年：4 March, 2014
• 年：2014
• 卷：22
• 期：3
• 页码：466-477
• 全文大小：2476 K

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Summary

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聽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.