Abstract
BackgroundThe 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.Methodology/Principal FindingsWe 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.Conclusion/SignificanceDiedel, 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.
Highlights
The innate immune system is our first line of defense against invading organisms while the adaptive immune system acts as a second line of defense
More effort has been expended on understanding the innate immune system, as it became clear that innate immunity is an evolutionarily ancient defense mechanism, which governs the initial detection of pathogens and stimulates the first line of host defense
The structure is composed of two subdomains, one of these belonging to the ferredoxin family fold
Summary
The innate immune system is our first line of defense against invading organisms while the adaptive immune system acts as a second line of defense. The innate immune system includes defenses that, for the most part, are constitutively present and ready to be mobilized upon infection It is not antigen-specific and reacts well to a variety of organisms. The JAK/STAT signal transduction pathway is conserved from insects to mammals and is involved in a wide variety of biological processes such as the cellular proliferation, the stem cell maintenance, the haematopoiesis and the innate immunity responses [9]. This pleiotropic cascade is the principal signaling mechanism for a large array of cytokines and growth factors in mammals. The CG11501 gene product, is a small protein of 115 residues with 10 cysteines
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