Structure of the retinal determination protein Dachshund reveals a DNA binding motif.
The Dachshund proteins are essential components of a regulatory network controlling cell fate determination. They have been implicated in eye, limb, brain, and muscle development. These proteins cannot be assigned to any recognizable structural or functional class based on amino acid sequence analysis. The 1.65 A crystal structure of the most conserved domain of human DACHSHUND is reported here. The protein forms an alpha/beta structure containing a DNA binding motif similar to that found in the winged helix/forkhead subgroup of the helix-turn-helix family. This unexpected finding alters the previously proposed molecular models for the role of Dachshund in the eye determination pathway. Furthermore, it provides a rational framework for future mechanistic analyses of the Dachshund proteins in several developmental contexts.
Kim
Seung-Sup
SS
Structural Biology Program, Skirball Institute, New York University Medical Center, New York, NY 10016, USA.
Zhang
Rong-guang
RG
Braunstein
Steve E
SE
Joachimiak
Andrzej
A
Cvekl
Ales
A
Hegde
Rashmi S
RS
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D005123:Eye / Q000196:embryology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics; D017385:Sequence Homology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human; C103968:dac protein, Drosophila; C060614:SKI protein, human; D004247:DNA