PDBsum entry 4bv4

Immune system

PDB id: 4bv4

Contents

Protein chains

66 a.a.

68 a.a.

440 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN-BMA-MAN-BMA

NAG ×4

Waters ×104

PDB id:

4bv4

Name:

Immune system

Title:

Structure and allostery in toll-spatzle recognition

Structure:

Protein spaetzlE C-106. Chain: l, m. Synonym: protein spaetzle. Engineered: yes. Protein toll, variable lymphocyte receptor b chimera. Chain: r. Fragment: protein toll, residues 28-397, variable lymphocyte receptor b, residues 133-201. Engineered: yes.

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Drosophila melanogaster, eptatretus burgeri. Fruit fly, inshore hagfish. Organism_taxid: 7227, 7764.

Resolution:

2.35Å R-factor: 0.197 R-free: 0.227

Authors:

M.F.Lewis,C.J.Arnot,H.Beeston,A.Mccoy,A.E.Ashcroft,N.J.Gay,M.Gangloff

Key ref:

M.Lewis et al. (2013). Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation. Proc Natl Acad Sci U S A, 110, 20461-20466. PubMed id: 24282309 DOI: 10.1073/pnas.1317002110

Date:

24-Jun-13 Release date: 04-Dec-13

Protein chain

P48607  (SPZ_DROME) -  Protein spaetzle from Drosophila melanogaster

Seq: 326 a.a.

Struc: 66 a.a.

Protein chain

P48607  (SPZ_DROME) -  Protein spaetzle from Drosophila melanogaster

Seq: 326 a.a.

Struc: 68 a.a.*

Protein chain

P08953  (TOLL_DROME) -  Protein toll from Drosophila melanogaster

Seq: 1097 a.a.

Struc: 440 a.a.*

Protein chain

Q4G1L2  (Q4G1L2_EPTBU) -  Variable lymphocyte receptor B from Eptatretus burgeri

Seq: 273 a.a.

Struc: 440 a.a.*

* PDB and UniProt seqs differ at 164 residue positions (black crosses)

DOI no: 10.1073/pnas.1317002110

Proc Natl Acad Sci U S A 110:20461-20466 (2013)

PubMed id: 24282309

Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation.

M.Lewis, C.J.Arnot, H.Beeston, A.McCoy, A.E.Ashcroft, N.J.Gay, M.Gangloff.

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.