PMID- 16049008
OWN - NLM
STAT- MEDLINE
DCOM- 20051128
LR  - 20220409
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 38
DP  - 2005 Sep 23
TI  - Dimerization of doublesex is mediated by a cryptic ubiquitin-associated domain 
      fold: implications for sex-specific gene regulation.
PG  - 32989-96
AB  - 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.
FAU - Bayrer, James R
AU  - Bayrer JR
AD  - Department of Biochemistry, Case Western Reserve University School of Medicine, 
      Cleveland, Ohio 44106, USA.
FAU - Zhang, Wei
AU  - Zhang W
FAU - Weiss, Michael A
AU  - Weiss MA
LA  - eng
SI  - PDB/1ZV1
GR  - T32 GM07250/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050727
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (DSX protein, Drosophila)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Transcription Factors)
RN  - 0 (Ubiquitin)
RN  - 9007-49-2 (DNA)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/chemistry
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Crystallography, X-Ray
MH  - DNA/chemistry
MH  - DNA-Binding Proteins/*chemistry
MH  - Dimerization
MH  - Drosophila Proteins/*chemistry
MH  - Drosophila melanogaster
MH  - Electrons
MH  - Female
MH  - *Gene Expression Regulation
MH  - Hydrogen Bonding
MH  - Male
MH  - Models, Biological
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Protein Conformation
MH  - Protein Folding
MH  - Protein Isoforms
MH  - Protein Structure, Tertiary
MH  - Sequence Homology, Amino Acid
MH  - Sex Factors
MH  - Transcription Factors/chemistry
MH  - Two-Hybrid System Techniques
MH  - Ubiquitin/*chemistry
EDAT- 2005/07/29 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/29 09:00
PHST- 2005/07/29 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/29 09:00 [entrez]
AID - S0021-9258(20)79158-1 [pii]
AID - 10.1074/jbc.M507990200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Sep 23;280(38):32989-96. doi: 10.1074/jbc.M507990200. Epub 2005 
      Jul 27.