4LXR

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

Summary for 4LXR

• Entry DOI: 10.2210/pdb4lxr/pdb
• Related: 3e07 4LXS
• Descriptor: Protein toll, Protein spaetzle C-106, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: tlr, leucine-rich repeat, immune system, cytokine receptor, embryonic development, innate immunity, receptor-ligand complex', immune system-cytokine complex, immune system/cytokine
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 3
• Total formula weight: 119557.35

Authors

Stelter, M.,Parthier, C.,Breithaupt, C.,Stubbs, M.T. (deposition date: 2013-07-30, release date: 2014-04-09, Last modification date: 2024-10-16)

Primary citation

Parthier, C.,Stelter, M.,Ursel, C.,Fandrich, U.,Lilie, H.,Breithaupt, C.,Stubbs, M.T.
Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity.
Proc.Natl.Acad.Sci.USA, 111:6281-6286, 2014

PubMed 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.

PubMed: 24733933
DOI: 10.1073/pnas.1320678111

Experimental method

X-RAY DIFFRACTION (2.2 Å)