4lxs

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Structure of the Toll - Spatzle complex, a molecular hub in Drosophila development and innate immunity (glycosylated form)Structure of the Toll - Spatzle complex, a molecular hub in Drosophila development and innate immunity (glycosylated form)

Structural highlights

4lxs is a 3 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , ,
Gene:Tl, CG5490 (DROME), spz, CG6134 (DROME)
Resources:FirstGlance, OCA, RCSB, PDBsum

Function

[SPZ_DROME] Component of the extracellular signaling pathway that establishes the dorsal-ventral pathway of the embryo. Three proteases; ndl, gd and snk process easter to create active easter. Active easter defines cell identities along the dorsal-ventral continuum by activating the spz ligand for the Tl receptor in the ventral region of the embryo. Spz C-106 in the hemolymph controls expression of the antifungal peptide Drosomycin (Drs) by acting as a ligand of Tl and inducing an intracellular signaling pathway.[1] [2] [3] [4]

Publication Abstract from PubMed

Drosophila Toll receptors are involved in embryonic development and the immune response of adult flies. In both processes, the only known Toll receptor ligand is the human nerve growth factor-like cystine knot protein Spatzle. Here we present the crystal structure of a 1:1 (nonsignaling) complex of the full-length Toll receptor ectodomain (ECD) with the Spatzle cystine knot domain dimer. The ECD is divided into two leucine-rich repeat (LRR) domains, each of which is capped by cysteine-rich domains. Spatzle binds to the concave surface of the membrane-distal LRR domain, in contrast to the flanking ligand interactions observed for mammalian Toll-like receptors, with asymmetric contributions from each Spatzle protomer. The structure allows rationalization of existing genetic and biochemical data and provides a framework for targeting the immune systems of insects of economic importance, as well as a variety of invertebrate disease vectors.

Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity.,Parthier C, Stelter M, Ursel C, Fandrich U, Lilie H, Breithaupt C, Stubbs MT Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6281-6. doi:, 10.1073/pnas.1320678111. Epub 2014 Apr 14. PMID:24733933[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Morisato D, Anderson KV. The spatzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. Cell. 1994 Feb 25;76(4):677-88. PMID:8124709
  2. ↑ DeLotto Y, Smith C, DeLotto R. Multiple isoforms of the Drosophila Spatzle protein are encoded by alternatively spliced maternal mRNAs in the precellular blastoderm embryo. Mol Gen Genet. 2001 Jan;264(5):643-52. PMID:11212919
  3. ↑ Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996 Sep 20;86(6):973-83. PMID:8808632
  4. ↑ Weber AN, Tauszig-Delamasure S, Hoffmann JA, Lelievre E, Gascan H, Ray KP, Morse MA, Imler JL, Gay NJ. Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat Immunol. 2003 Aug;4(8):794-800. Epub 2003 Jul 20. PMID:12872120 doi:http://dx.doi.org/10.1038/ni955
  5. ↑ Parthier C, Stelter M, Ursel C, Fandrich U, Lilie H, Breithaupt C, Stubbs MT. Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity. Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6281-6. doi:, 10.1073/pnas.1320678111. Epub 2014 Apr 14. PMID:24733933 doi:http://dx.doi.org/10.1073/pnas.1320678111

4lxs, resolution 3.30Å

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