Structure of the Toll-Spätzle complex, a molecular hub in Drosophila development and innate immunity

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 17, 2014, Pages 6281-6286

  Parthier, Christoph ^a   Stelter, Marco ^a   Ursel, Christian ^a   Fandrich, Uwe ^a   Lilie, Hauke ^a   Breithaupt, Constanze ^a   Stubbs, Milton T ^a  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

Embryonic morphogenesis; Protein evolution; Toll signaling

Indexed keywords

CYSTEINE; DIMER; LEUCINE; TOLL LIKE RECEPTOR; TOLL SPATZLE COMPLEX; UNCLASSIFIED DRUG; DROSOPHILA PROTEIN; SPATZLE PROTEIN, DROSOPHILA; TL PROTEIN, DROSOPHILA;

AMINO TERMINAL SEQUENCE; ARTICLE; BETA SHEET; COMPLEX FORMATION; CRYSTAL STRUCTURE; CRYSTALLIZATION; DISEASE CARRIER; DROSOPHILA MELANOGASTER; EMBRYO DEVELOPMENT; GLYCOSYLATION; HYDROGEN BOND; INNATE IMMUNITY; LIGAND BINDING; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN SECONDARY STRUCTURE; STOICHIOMETRY; SURFACE PROPERTY; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; EMBRYONIC MORPHOGENESIS; GROWTH, DEVELOPMENT AND AGING; HUMAN; IMMUNOLOGY; METABOLISM; PROTEIN EVOLUTION; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE; SIGNAL TRANSDUCTION; TOLL SIGNALING;

EMBRYONIC MORPHOGENESIS; PROTEIN EVOLUTION; TOLL SIGNALING;

ANIMALS; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; HUMANS; IMMUNITY, INNATE; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 84899621123     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1320678111     Document Type: Article

References (54)

1. Anderson KV, Nüsslein-Volhard C (1984) Information for the dorsal-ventral pattern of the Drosophila embryo is stored as maternal mRNA. Nature 311(5983):223-227.
2. Anderson KV, Bokla L, Nüsslein-Volhard C (1985) Establishment of dorsal-ventral polarity in the Drosophila embryo: The induction of polarity by the Toll gene product. Cell 42(3):791-798.
3. Anderson KV, Jürgens G, Nüsslein-Volhard C (1985) Establishment of dorsal-ventral polarity in the Drosophila embryo: Genetic studies on the role of the Toll gene product. Cell 42(3):779-789.
4. Hashimoto C, Hudson KL, Anderson KV (1988) The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 52(2):269-279.
5. Imler JL, Hoffmann JA (2001) Toll receptors in innate immunity. Trends Cell Biol 11(7): 304-311.
6. Schneider DS, Hudson KL, Lin TY, Anderson KV (1991) Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo. Genes Dev 5(5):797-807.
7. Gay NJ, Keith FJ (1991) Drosophila Toll and IL-1 receptor. Nature 351(6325):355-356.
8. Schneider DS, Jin YS, Morisato D, Anderson KV (1994) A processed form of the Spätzle protein defines dorsal-ventral polarity in the Drosophila embryo. Development 120(5): 1243-1250.
9. Stein D, Roth S, Vogelsang E, Nüsslein-Volhard C (1991) The polarity of the dorsoventral axis in the Drosophila embryo is defined by an extracellular signal. Cell 65(5): 725-735.
10. DeLotto Y, DeLotto R (1998) Proteolytic processing of the Drosophila Spätzle protein by easter generates a dimeric NGF-like molecule with ventralising activity. Mech Dev 72(1-2):141-148.
11. LeMosy EK, Hong CC, Hashimoto C (1999) Signal transduction by a protease cascade. Trends Cell Biol 9(3):102-107.
12. Morisato D, Anderson KV (1995) Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo. Annu Rev Genet 29:371-399.
13. Moussian B, Roth S (2005) Dorsoventral axis formation in the Drosophila embryo: Shaping and transducing a morphogen gradient. Curr Biol 15(21):R887-R899.
14. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86(6):973-983.
15. Medzhitov R, Preston-Hurlburt P, Janeway CA, Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388(6640): 394-397.
16. Poltorak A, et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science 282(5396):2085-2088.
17. Gay NJ, Gangloff M (2007) Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76:141-165.
18. Botos I, Segal DM, Davies DR (2011) The structural biology of Toll-like receptors. Structure 19(4):447-459.
19. Kang JY, Lee JO (2011) Structural biology of the Toll-like receptor family. Annu Rev Biochem 80:917-941.
20. Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T (2013) Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science 339(6126):1426-1429.
21. Yoon SI, et al. (2012) Structural basis of TLR5-flagellin recognition and signaling. Science 335(6070):859-864.
22. Sun H, Towb P, Chiem DN, Foster BA, Wasserman SA (2004) Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral patterning. EMBO J 23(1): 100-110.
23. Tauszig S, Jouanguy E, Hoffmann JA, Imler JL (2000) Toll-related receptors and the control of antimicrobial peptide expression in Drosophila. Proc Natl Acad Sci USA 97(19):10520-10525.
24. McIlroy G, et al. (2013) Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS. Nat Neurosci 16(9):1248-1256.
25. Jang IH, et al. (2006) A Spätzle-processing enzyme required for toll signaling activation in Drosophila innate immunity. Dev Cell 10(1):45-55.
26. DeLotto Y, Smith C, DeLotto R (2001) Multiple isoforms of the Drosophila Spätzle protein are encoded by alternatively spliced maternal mRNAs in the precellular blastoderm embryo. Mol Gen Genet 264(5):643-652.
27. Hoffmann A, et al. (2008) Biophysical characterization of refolded Drosophila Spätzle, a cystine knot protein, reveals distinct properties of three isoforms. J Biol Chem 283(47):32598-32609.
28. Ursel C, et al. (2013) In vitro maturation of Drosophila melanogaster Spätzle protein with refolded Easter reveals a novel cleavage site within the prodomain. Biol Chem 394(8):1069-1075.
29. Weber ANR, et al. (2007) Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand. J Biol Chem 282(18):13522-13531.
30. Mizuguchi K, Parker JS, Blundell TL, Gay NJ (1998) Getting knotted: A model for the structure and activation of Spätzle. Trends Biochem Sci 23(7):239-242.
31. Weber ANR, et al. (2003) Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling. Nat Immunol 4(8):794-800.
32. Weber ANR, Moncrieffe MC, Gangloff M, Imler JL, Gay NJ (2005) Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway. J Biol Chem 280(24):22793-22799.
33. Stelter M, et al. (2013) High level expression of the Drosophila Toll receptor ectodomain and crystallization of its complex with the morphogen Spätzle. Biol Chem 394(8):1091-1096.
34. Gangloff M, et al. (2008) Structural insight into the mechanism of activation of the Toll receptor by the dimeric ligand Spätzle. J Biol Chem 283(21):14629-14635.
35. Gangloff M, Arnot CJ, Lewis M, Gay NJ (2013) Functional insights from the crystal structure of the N-terminal domain of the prototypical Toll receptor. Structure 21(1): 143-153.
36. Bella J, Hindle KL, McEwan PA, Lovell SC (2008) The leucine-rich repeat structure. Cell Mol Life Sci 65(15):2307-2333.
37. Buchanan SG, Gay NJ (1996) Structural and functional diversity in the leucine-rich repeat family of proteins. Prog Biophys Mol Biol 65(1-2):1-44.
38. Kim HM, et al. (2007) Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130(5):906-917.
39. Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11(6):725-732.
40. Arnot CJ, Gay NJ, Gangloff M (2010) Molecular mechanism that induces activation of Spätzle, the ligand for the Drosophila Toll receptor. J Biol Chem 285(25):19502-19509.
41. Wang Y, Zhu S (2009) Evolutionary and functional epitopes of the Spätzle protein: New insights into activation of the Toll receptor. Cell Mol Life Sci 66(9):1595-1602.
42. Hu XD, Yagi Y, Tanji T, Zhou SL, Ip YT (2004) Multimerization and interaction of Toll and Spätzle in Drosophila. Proc Natl Acad Sci USA 101(25):9369-9374.
43. Liu L, et al. (2008) Structural basis of Toll-like receptor 3 signaling with doublestranded RNA. Science 320(5874):379-381.
44. Kobe B, Deisenhofer J (1995) A structural basis of the interactions between leucinerich repeats and protein ligands. Nature 374(6518):183-186.
45. Fan QR, Hendrickson WA (2005) Structure of human follicle-stimulating hormone in complex with its receptor. Nature 433(7023):269-277.
46. Jiang X, et al. (2012) Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc Natl Acad Sci USA 109(31):12491-12496.
47. Gavutis M, Jaks E, Lamken P, Piehler J (2006) Determination of the two-dimensional interaction rate constants of a cytokine receptor complex. Biophys J 90(9):3345-3355.
48. Park BS, et al. (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458(7242):1191-1195.
49. Tong Q, et al. (2012) Structural and functional insights into lipid-bound nerve growth factors. FASEB J 26(9):3811-3821.
50. Shilo BZ, Haskel-Ittah M, Ben-Zvi D, Schejter ED, Barkai N (2013) Creating gradients by morphogen shuttling. Trends Genet 29(6):339-347.
51. Morisato D (2001) Spätzle regulates the shape of the dorsal gradient in the Drosophila embryo. Development 128(12):2309-2319.
52. Haskel-Ittah M, et al. (2012) Self-organized shuttling: Generating sharp dorsoventral polarity in the early Drosophila embryo. Cell 150(5):1016-1028.
53. Morisato D, Anderson KV (1994) The spätzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. Cell 76(4):677-688.
54. Lewis M, et al. (2013) Cytokine Spätzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation. Proc Natl Acad Sci USA 110(51):20461-20466.