2wty
From Proteopedia
Crystal structure of the homodimeric MafB in complex with the T-MARE binding site
Structural highlights
FunctionMAFB_MOUSE Acts as a transcriptional activator or repressor. Plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe 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. Design of a bZip Transcription Factor with Homo/Heterodimer-Induced DNA-Binding Preference.,Pogenberg V, Consani Textor L, Vanhille L, Holton SJ, Sieweke MH, Wilmanns M Structure. 2014 Feb 11. pii: S0969-2126(14)00009-4. doi:, 10.1016/j.str.2013.12.017. PMID:24530283[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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