PDBsum entry 4lxr

Immune system/cytokine

PDB id: 4lxr

Contents

Protein chains

755 a.a.

64 a.a.

66 a.a.

Ligands

NAG-NAG-BMA-BMA-MAN

NAG-NAG ×2

NAG-NAG-BMA

NAG ×6

EPE

Waters ×504

PDB id:

4lxr

Name:

Immune system/cytokine

Title:

Structure of the toll - spatzle complex, a molecular hub in drosophila development and innate immunity

Structure:

Protein toll. Chain: a. Fragment: unp residues 28-802. Engineered: yes. Protein spaetzlE C-106. Chain: j, k. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: tl, cg5490. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Gene: spz, cg6134. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.178 R-free: 0.218

Authors:

M.Stelter,C.Parthier,C.Breithaupt,M.T.Stubbs

Key ref:

C.Parthier et al. (2014). Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity. Proc Natl Acad Sci U S A, 111, 6281-6286. PubMed id: 24733933 DOI: 10.1073/pnas.1320678111

Date:

30-Jul-13 Release date: 09-Apr-14

Protein chain

P08953  (TOLL_DROME) -  Protein toll from Drosophila melanogaster

Seq: 1097 a.a.

Struc: 755 a.a.

Protein chain

P48607  (SPZ_DROME) -  Protein spaetzle from Drosophila melanogaster

Seq: 326 a.a.

Struc: 64 a.a.

Protein chain

P48607  (SPZ_DROME) -  Protein spaetzle from Drosophila melanogaster

Seq: 326 a.a.

Struc: 66 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.2.2.6 - ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
• Reaction: NAD⁺ + H2O = ADP-D-ribose + nicotinamide + H⁺

NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+) (Bound ligand (Het Group name = NAG) matches with 43.75% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.1320678111

Proc Natl Acad Sci U S A 111:6281-6286 (2014)

PubMed id: 24733933

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

C.Parthier, M.Stelter, C.Ursel, U.Fandrich, H.Lilie, C.Breithaupt, M.T.Stubbs.

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.