title: Crystal structure of Diedel, a marker of the immune response of Drosophila melanogaster.
abstract: BACKGROUND
  The Drosophila melanogaster gene CG11501 is up regulated after a septic injury and was proposed to act as a negative regulator of the JAK/STAT signaling pathway. Diedel, the CG11501 gene product, is a small protein of 115 residues with 10 cysteines.
  
  
  RESULTS
  We have produced Diedel in Drosophila S2 cells as an extra cellular protein thanks to its own signal peptide and solved its crystal structure at 1.15 Å resolution by SIRAS using an iodo derivative. Diedel is composed of two sub domains SD1 and SD2. SD1 is made of an antiparallel β-sheet covered by an α-helix and displays a ferredoxin-like fold. SD2 reveals a new protein fold made of loops connected by four disulfide bridges. Further structural analysis identified conserved hydrophobic residues on the surface of Diedel that may constitute a potential binding site. The existence of two conformations, cis and trans, for the proline 52 may be of interest as prolyl peptidyl isomerisation has been shown to play a role in several physiological mechanisms. The genome of D. melanogaster contains two other genes coding for proteins homologous to Diedel, namely CG43228 and CG34329. Strikingly, apart from Drosophila and the pea aphid Acyrthosiphon pisum, Diedel-related sequences were exclusively identified in a few insect DNA viruses of the Baculoviridae and Ascoviridae families.
  
  
  CONCLUSIONS
  Diedel, a marker of the Drosophila antimicrobial/antiviral response, is a member of a small family of proteins present in drosophilids, aphids and DNA viruses infecting lepidopterans. Diedel is an extracellular protein composed of two sub-domains. Two special structural features (hydrophobic surface patch and cis/trans conformation for proline 52) may indicate a putative interaction site, and support an extra cellular signaling function for Diedel, which is in accordance with its proposed role as negative regulator of the JAK/STAT signaling pathway.
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR4301, Orléans, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Coste
authors.forename: Cordula
authors.initials: C
authors.lastname: Kemp
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bobezeau
authors.forename: Charles
authors.initials: C
authors.lastname: Hetru
authors.forename: Christine
authors.initials: C
authors.lastname: Kellenberger
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
authors.forename: Alain
authors.initials: A
authors.lastname: Roussel
mesh_terms: D000818:Animals; D001042:Aphids / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D004331:Drosophila melanogaster; D053612:Janus Kinases / Q000737:chemistry / Q000276:immunology; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D050791:STAT Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000737:chemistry / Q000276:immunology
chemical_list: D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; D053612:Janus Kinases; C085845:hop protein, Drosophila