1zv1
From Proteopedia
Crystal structure of the dimerization domain of doublesex protein from D. melanogaster
Structural highlights
Function[DSX_DROME] Controls somatic sexual differentiation. Binds directly and specifically to the FBE (fat body enhancer) of the yolk protein 1 and 2 genes (Yp1 and Yp2). This enhancer is sufficient to direct the female-specific transcription characteristic of the Yp genes in adult fat bodies. Involved in regulation of male-specific expression of takeout in brain-associated fat body.[1] 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 PubMedMale- and female-specific isoforms of the Doublesex (DSX) transcription factor regulate somatic sexual differentiation in Drosophila. The isoforms (DSX(M) and DSX(F)) share an N-terminal DNA binding domain (the DM motif), broadly conserved among metazoan sex-determining pathways. DM-DNA recognition is enhanced by a C-terminal dimerization domain. The crystal structure of this domain, determined at a resolution of 1.6 A, reveals a novel dimeric arrangement of ubiquitin-associated (UBA) folds. Although this alpha-helical motif is well characterized in pathways of DNA repair and subcellular trafficking, to our knowledge this is its first report in a transcription factor. Dimerization is mediated by a non-canonical hydrophobic interface extrinsic to the putative ubiquitin binding surface. Key side chains at this interface, identified by alanine scanning mutagenesis, are conserved among DSX homologs. The mechanism of dimerization is thus unrelated to the low affinity domain swapping observed among ubiquitin-associated CUE domains. The unexpected observation of a ubiquitin-associated fold in DSX extends the repertoire of alpha-helical dimerization elements in transcription factors. The possibility that the ubiquitination machinery participates in the regulation of sexual dimorphism is discussed. Dimerization of doublesex is mediated by a cryptic ubiquitin-associated domain fold: implications for sex-specific gene regulation.,Bayrer JR, Zhang W, Weiss MA J Biol Chem. 2005 Sep 23;280(38):32989-96. Epub 2005 Jul 27. PMID:16049008[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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