title: Crystal structure of the dachshund homology domain of human SKI.
abstract: The nuclear protooncoprotein SKI negatively regulates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. It directly interacts with the Smads and, by various mechanisms, represses the transcription of TGF-beta-responsive genes. SKI is a multidomain protein that includes a domain bearing high sequence similarity with the retinal determination protein Dachshund (the Dachshund homology domain, DHD). The SKI-DHD has been implicated in SMAD-2/3, N-CoR, SKIP, and PML-RARalpha binding. The 1.65 A crystal structure of the Dachshund homology domain of human SKI is reported here. The SKI-DHD adopts a mixed alpha/beta structure which includes features found in the forkhead/winged-helix family of DNA binding proteins, although SKI-DHD is not a DNA binding domain. Residues that form a contiguous surface patch on SKI-DHD are conserved within the Ski/Sno family and with Dachshund, suggesting that this domain may mediate intermolecular interactions common to these proteins.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Margarita
authors.initials: M
authors.lastname: Malakhova
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.forename: Rashmi S
authors.initials: RS
authors.lastname: Hegde
mesh_terms: D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors
chemical_list: C486747:DACH1 protein, human; C403064:DACH2 protein, human; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C060614:SKI protein, human