First Author | Pogenberg V | Year | 2014 |
Journal | Structure | Volume | 22 |
Issue | 3 | Pages | 466-77 |
PubMed ID | 24530283 | Mgi Jnum | J:247422 |
Mgi Id | MGI:5926790 | Doi | 10.1016/j.str.2013.12.017 |
Citation | Pogenberg V, et al. (2014) Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference. Structure 22(3):466-77 |
abstractText | 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. |