Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1.
Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. Previously we have revealed a five-helix structure of the N-terminal CUT domain, which is essentially the folded region in the MAR-binding domain, of human SATB1 by NMR. Here we determined crystal structure of the complex of the CUT domain and a MAR DNA, in which the third helix of the CUT domain deeply enters the major groove of DNA in the B-form. Bases of 5'-CTAATA-3' sequence are contacted by this helix, through direct and water-mediated hydrogen bonds and apolar and van der Waals contacts. Mutations at conserved base-contacting residues, Gln402 and Gly403, reduced the DNA-binding activity, which confirmed the importance of the observed interactions involving these residues. A significant number of equivalent contacts are observed also for typically four-helix POU-specific domains of POU-homologous proteins, indicating that these domains share a common framework of the DNA-binding mode, recognizing partially similar DNA sequences.
Yamasaki
Kazuhiko
K
Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. yamasaki@aist.go.jp
Akiba
Toshihiko
T
Yamasaki
Tomoko
T
Harata
Kazuaki
K
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D019143:Evolution, Molecular; D036961:Matrix Attachment Region Binding Proteins / Q000737:chemistry* / Q000235:genetics; D045170:Matrix Attachment Regions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D017385:Sequence Homology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics
D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human; D014157:Transcription Factors; D004247:DNA