4BV4

Structure and allostery in Toll-Spatzle recognition

Summary for 4BV4

• Entry DOI: 10.2210/pdb4bv4/pdb
• Descriptor: PROTEIN SPAETZLE C-106, PROTEIN TOLL, VARIABLE LYMPHOCYTE RECEPTOR B CHIMERA, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: cytokine recognition, embryonic development, immune system, innate immunity, leucine-rich repeats, cystine-knot, glycoprotein
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY); More
• Total number of polymer chains: 3
• Total formula weight: 77017.04

Authors

Lewis, M.F.,Arnot, C.J.,Beeston, H.,McCoy, A.,Ashcroft, A.E.,Gay, N.J.,Gangloff, M. (deposition date: 2013-06-24, release date: 2013-12-04, Last modification date: 2024-10-09)

Primary citation

Lewis, M.,Arnot, C.J.,Beeston, H.,Mccoy, A.,Ashcroft, A.E.,Gay, N.J.,Gangloff, M.
Cytokine Spatzle Binds to the Drosophila Immunoreceptor Toll with a Neurotrophin-Like Specificity and Couples Receptor Activation.
Proc.Natl.Acad.Sci.USA, 110:20461-, 2013

PubMed Abstract: Drosophila Toll functions in embryonic development and innate immunity and is activated by an endogenous ligand, Spätzle (Spz). The related Toll-like receptors in vertebrates also function in immunity but are activated directly by pathogen-associated molecules such as bacterial endotoxin. Here, we present the crystal structure at 2.35-Å resolution of dimeric Spz bound to a Toll ectodomain encompassing the first 13 leucine-rich repeats. The cystine knot of Spz binds the concave face of the Toll leucine-rich repeat solenoid in an area delineated by N-linked glycans and induces a conformational change. Mutagenesis studies confirm that the interface observed in the crystal structure is relevant for signaling. The asymmetric binding mode of Spz to Toll is similar to that of nerve growth factor (NGF) in complex with the p75 neurotrophin receptor but is distinct from that of microbial ligands bound to the Toll-like receptors. Overall, this study indicates an allosteric signaling mechanism for Toll in which ligand binding to the N terminus induces a conformational change that couples to homodimerization of juxtamembrane structures in the Toll ectodomain C terminus.

PubMed: 24282309
DOI: 10.1073/PNAS.1317002110

Experimental method

X-RAY DIFFRACTION (2.35 Å)