1zv1

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Crystal structure of the dimerization domain of doublesex protein from D. melanogaster

File:1zv1.gif


1zv1, resolution 1.60Å

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OverviewOverview

Male- 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.

About this StructureAbout this Structure

1ZV1 is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

ReferenceReference

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

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