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protein metals links
Transcription PDB id
1lpv
Jmol
Contents
Protein chain
52 a.a. *
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1lpv
Name: Transcription
Title: Drosophila melanogaster doublesex (dsx), nmr, 18 structures
Structure: Doublesex protein. Chain: a. Engineered: yes
Source: Synthetic: yes. Other_details: the sequence naturally occurs in drosophila melanogaster (fruit fly).
NMR struc: 18 models
Authors: L.Zhu,J.Wilken,N.Phillips,U.Narendra,G.Chan,S.Stratton, S.Kent,M.A.Weiss
Key ref: L.Zhu et al. (2000). Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers. Genes Dev, 14, 1750-1764. PubMed id: 10898790 Ref: Full text
Date:
08-May-02     Release date:   02-Oct-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23023  (DSX_DROME) -  Protein doublesex
Seq:
Struc: 		 
Seq:
Struc: 		549 a.a.
52 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     sex differentiation   2 terms 
  Biochemical function     sequence-specific DNA binding     1 term  

 

 
Full text Genes Dev 14:1750-1764 (2000)
PubMed id: 10898790  
 
 
Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers.
L.Zhu, J.Wilken, N.B.Phillips, U.Narendra, G.Chan, S.M.Stratton, S.B.Kent, M.A.Weiss.
 
  ABSTRACT  
 
Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, remarkably, are associated with human sex reversal (46, XY gonadal dysgenesis). Here we demonstrate that the structure of the Doublesex domain contains a novel zinc module and disordered tail. The module consists of intertwined CCHC and HCCC Zn(2+)-binding sites; the tail functions as a nascent recognition alpha-helix. Mutations in either Zn(2+)-binding site or tail can lead to an intersex phenotype. The motif binds in the DNA minor groove without sharp DNA bending. These molecular features, unusual among zinc fingers and zinc modules, underlie the organization of a Drosophila enhancer that integrates sex- and tissue-specific signals. The structure provides a foundation for analysis of DM mutations affecting sexual dimorphism and courtship behavior.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21281449 A.Herpin, and M.Schartl (2011).
Dmrt1 genes at the crossroads: a widespread and central class of sexual development factors in fish.
  FEBS J, 278, 1010-1019.  
20877001 J.N.Shukla, and J.Nagaraju (2010).
Doublesex: a conserved downstream gene controlled by diverse upstream regulators.
  J Genet, 89, 341-356.  
20616082 M.W.Murphy, A.L.Sarver, D.Rice, K.Hatzi, K.Ye, A.Melnick, L.L.Heckert, D.Zarkower, and V.J.Bardwell (2010).
Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis.
  Proc Natl Acad Sci U S A, 107, 13360-13365.  
20368965 T.Sato, D.Rocancourt, L.Marques, S.Thorsteinsdóttir, and M.Buckingham (2010).
A Pax3/Dmrt2/Myf5 regulatory cascade functions at the onset of myogenesis.
  PLoS Genet, 6, e1000897.  
19523063 D.C.Oliveira, J.H.Werren, E.C.Verhulst, J.D.Giebel, A.Kamping, L.W.Beukeboom, and L.van de Zande (2009).
Identification and characterization of the doublesex gene of Nasonia.
  Insect Mol Biol, 18, 315-324.  
18992257 N.Narayana, and M.A.Weiss (2009).
Crystallographic analysis of a sex-specific enhancer element: sequence-dependent DNA structure, hydration, and dynamics.
  J Mol Biol, 385, 469-490.
PDB code: 3bse
19067156 S.Klinbunga, P.Amparyup, B.Khamnamtong, I.Hirono, T.Aoki, and P.Jarayabhand (2009).
Isolation and characterization of testis-specific DMRT1 in the tropical abalone (Haliotis asinina).
  Biochem Genet, 47, 66-79.  
18685240 H.Hoshi, and A.Nakao (2008).
Molecular cloning of full-length Dmrt1 cDNA of Reeves turtle (Chinemys reevesii).
  J Vet Med Sci, 70, 687-692.  
17967886 M.G.Suzuki, S.Imanishi, N.Dohmae, T.Nishimura, T.Shimada, and S.Matsumoto (2008).
Establishment of a novel in vivo sex-specific splicing assay system to identify a trans-acting factor that negatively regulates splicing of Bombyx mori dsx female exons.
  Mol Cell Biol, 28, 333-343.  
18606452 S.Fields, K.Ternyak, H.Gao, R.Ostraat, J.Akerlund, and J.Hagman (2008).
The 'zinc knuckle' motif of Early B cell Factor is required for transcriptional activation of B cell-specific genes.
  Mol Immunol, 45, 3786-3796.  
18493064 T.L.Turner, M.T.Levine, M.L.Eckert, and D.J.Begun (2008).
Genomic analysis of adaptive differentiation in Drosophila melanogaster.
  Genetics, 179, 455-473.  
17760954 A.Herpin, D.Schindler, A.Kraiss, U.Hornung, C.Winkler, and M.Schartl (2007).
Inhibition of primordial germ cell proliferation by the medaka male determining gene Dmrt I bY.
  BMC Dev Biol, 7, 99.  
17605809 M.W.Murphy, D.Zarkower, and V.J.Bardwell (2007).
Vertebrate DM domain proteins bind similar DNA sequences and can heterodimerize on DNA.
  BMC Mol Biol, 8, 58.  
17567962 N.Lei, K.I.Hornbaker, D.A.Rice, T.Karpova, V.A.Agbor, and L.L.Heckert (2007).
Sex-specific differences in mouse DMRT1 expression are both cell type- and stage-dependent during gonad development.
  Biol Reprod, 77, 466-475.  
17029221 A.Kanamori, A.Yamamura, S.Koshiba, J.S.Lee, E.F.Orlando, and H.Hori (2006).
Methyltestosterone efficiently induces male development in the self-fertilizing hermaphrodite fish, Kryptolebias marmoratus.
  Genesis, 44, 495-503.  
16272418 M.D.Drapeau, S.A.Cyran, M.M.Viering, P.K.Geyer, and A.D.Long (2006).
A cis-regulatory sequence within the yellow locus of Drosophila melanogaster required for normal male mating success.
  Genetics, 172, 1009-1030.  
16382145 W.Zhang, B.Li, R.Singh, U.Narendra, L.Zhu, and M.A.Weiss (2006).
Regulation of sexual dimorphism: mutational and chemogenetic analysis of the doublesex DM domain.
  Mol Cell Biol, 26, 535-547.  
15213406 J.Bayrer, Z.Wan, B.Li, and M.A.Weiss (2004).
Expression, crystallization and preliminary X-ray characterization of the Drosophila transcription factor Doublesex.
  Acta Crystallogr D Biol Crystallogr, 60, 1328-1330.  
15376325 T.Kobayashi, M.Matsuda, H.Kajiura-Kobayashi, A.Suzuki, N.Saito, M.Nakamoto, N.Shibata, and Y.Nagahama (2004).
Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes.
  Dev Dyn, 231, 518-526.  
  12683972 J.N.Volff, M.Kondo, and M.Schartl (2003).
Medaka dmY/dmrt1Y is not the universal primary sex-determining gene in fish.
  Trends Genet, 19, 196-199.  
12077294 A.B.Dean, M.J.Stanger, J.T.Dansereau, P.Van Roey, V.Derbyshire, and M.Belfort (2002).
Zinc finger as distance determinant in the flexible linker of intron endonuclease I-TevI.
  Proc Natl Acad Sci U S A, 99, 8554-8561.  
12193652 I.Nanda, M.Kondo, U.Hornung, S.Asakawa, C.Winkler, A.Shimizu, Z.Shan, T.Haaf, N.Shimizu, A.Shima, M.Schmid, and M.Schartl (2002).
A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of the medaka, Oryzias latipes.
  Proc Natl Acad Sci U S A, 99, 11778-11783.  
12183618 K.C.Burtis (2002).
Development. Doublesex in the middle.
  Science, 297, 1135-1136.  
12231628 R.Lints, and S.W.Emmons (2002).
Regulation of sex-specific differentiation and mating behavior in C. elegans by a new member of the DM domain transcription factor family.
  Genes Dev, 16, 2390-2402.  
11932949 X.Huang, H.Cheng, Y.Guo, L.Liu, J.Gui, and R.Zhou (2002).
A conserved family of doublesex-related genes from fishes.
  J Exp Zool, 294, 63-67.  
11179890 J.H.Laity, B.M.Lee, and P.E.Wright (2001).
Zinc finger proteins: new insights into structural and functional diversity.
  Curr Opin Struct Biol, 11, 39-46.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.