2wt7
Crystal structure of the bZIP heterodimeric complex MafB:cFos bound to DNACrystal structure of the bZIP heterodimeric complex MafB:cFos bound to DNA
Structural highlights
FunctionFOS_MOUSE Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling (By similarity). Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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