Structural highlights
Function[SOX4_MOUSE] Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif. Publication Abstract from PubMedIt has recently been proposed that the sequence preferences of DNA-binding transcription factors can be well described by models that include the positional interdependence of the nucleotides of the target sites. Such binding models allow for multiple motifs to be invoked, such as principal and secondary motifs differing at two or more nucleotide positions. However, the structural mechanisms underlying the accommodation of such variant motifs by TFs remain elusive. Here we present the crystal structure of the high-mobility group (HMG) domain of Sox4 bound to DNA. By comparing this structure with previously solved structures of Sox17 and Sox2 we observed subtle conformational differences at the DNA binding interface. Furthermore, using quantitative electrophoretic mobility shift assays (EMSAs) we validated the positional interdependence of two nucleotides and the presence of a secondary Sox motif in the affinity landscape of Sox4. These data suggest that a concerted rearrangement of two interface amino acids enables Sox4 to accommodate primary and secondary motifs. The structural adoptions lead to altered dinucleotide preferences that mutually reinforce each other. These analyses underline the complexity of the DNA recognition by TFs and provide an experimental validation for the conceptual framework of positional interdependence and secondary binding motifs. Crystal structure of the Sox4 HMG/DNA complex suggests a mechanism for the positional interdependence in DNA recognition.,Jauch R, Ng CK, Narasimhan K, Kolatkar PR Biochem J. 2011 Dec 19. PMID:22181698[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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