title: Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity.
abstract: 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 Spätzle. Here we present the crystal structure of a 1:1 (nonsignaling) complex of the full-length Toll receptor ectodomain (ECD) with the Spätzle cystine knot domain dimer. The ECD is divided into two leucine-rich repeat (LRR) domains, each of which is capped by cysteine-rich domains. Spätzle 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 Spätzle 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.
authors.affiliation: Institut für Biochemie und Biotechnologie and Mitteldeutsches Zentrum für Struktur und Dynamik von Proteinen, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle (Saale), Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Parthier
authors.forename: Marco
authors.initials: M
authors.lastname: Stelter
authors.forename: Christian
authors.initials: C
authors.lastname: Ursel
authors.forename: Uwe
authors.initials: U
authors.lastname: Fandrich
authors.forename: Hauke
authors.initials: H
authors.lastname: Lilie
authors.forename: Constanze
authors.initials: C
authors.lastname: Breithaupt
authors.forename: Milton T
authors.initials: MT
authors.lastname: Stubbs
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C086179:spz protein, Drosophila
keywords: Toll signaling; embryonic morphogenesis; protein evolution
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