PDBsum entry: 2cb3

Immune system

PDB id: 2cb3

Contents

Protein chains

171 a.a. *

Ligands

GOL

MLD ×4

Waters ×205

* Residue conservation analysis

PDB id:

2cb3

Name:

Immune system

Title:

Crystal structure of peptidoglycan recognition protein-le in complex with tracheal cytotoxin (monomeric diaminopimelic acid-type peptidoglycan)

Structure:

Peptidoglycan-recognition protein-le. Chain: a, b, c, d. Fragment: residues 173-345. Engineered: yes. Mutation: yes. Other_details: peptidoglycan recognition protein-le in complex with tracheal cytotoxin

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.40Å R-factor: 0.198 R-free: 0.214

Authors:

J.-H.Lim,M.-S.Kim,B.-H.Oh

Key ref:

J.H.Lim et al. (2006). Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins. J Biol Chem, 281, 8286-8295. PubMed id: 16428381 DOI: 10.1074/jbc.M513030200

Date:

29-Dec-05 Release date: 26-Jan-06

Protein chains

Q9VXN9  (PGPLE_DROME) -  Peptidoglycan-recognition protein LE

Seq: 345 a.a.

Struc: 171 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Biological process: peptidoglycan catabolic process (1 term)
• Biochemical function: protein binding (2 terms)

DOI no: 10.1074/jbc.M513030200

J Biol Chem 281:8286-8295 (2006)

PubMed id: 16428381

Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins.

J.H.Lim, M.S.Kim, H.E.Kim, T.Yano, Y.Oshima, K.Aggarwal, W.E.Goldman, N.Silverman, S.Kurata, B.H.Oh.

ABSTRACT

Drosophila peptidoglycan recognition protein (PGRP)-LCx and -LCa are receptors that preferentially recognize meso-diaminopimelic acid (DAP)-type peptidoglycan (PGN) present in Gram-negative bacteria over lysine-type PGN of gram-positive bacteria and initiate the IMD signaling pathway, whereas PGRP-LE plays a synergistic role in this process of innate immune defense. How these receptors can distinguish the two types of PGN remains unclear. Here the structure of the PGRP domain of Drosophila PGRP-LE in complex with tracheal cytotoxin (TCT), the monomeric DAP-type PGN, reveals a buried ionic interaction between the unique carboxyl group of DAP and a previously unrecognized arginine residue. This arginine is conserved in the known DAP-type PGN-interacting PGRPs and contributes significantly to the affinity of the protein for the ligand. Unexpectedly, TCT induces infinite head-to-tail dimerization of PGRP-LE, in which the disaccharide moiety, but not the peptide stem, of TCT is positioned at the dimer interface. A sequence comparison suggests that TCT induces heterodimerization of the ectodomains of PGRP-LCx and -LCa in a closely analogous manner to prime the IMD signaling pathway, except that the heterodimer formation is nonperpetuating.

Selected figure(s)

Figure 2.
FIGURE 2. TCT induces the formation of infinitely long oligomers of PGRP-LE. a, native gel electrophoresis. The addition of TCT induces the formation of nondiscrete oligomers of PGRP-LE, whose sizes increase proportionally with the concentration of TCT. b, formation of an infinitely long oligomer in a head-to-tail fashion. Four molecules of the PGRP-LE·TCT complex in the crystal structure are sequentially stacked to emphasize the head-to-tail oligomerization of the protein induced by TCT binding. Each monomer of PGRP-LE is shown in a different color. Helix 1, which provides most of the dimerizing interactions, is shown as a ribbon. The bound TCT is shown in ball-and-stick representations. The residues in contact with the dimerizing PGRP-LE molecule are highlighted by a different color on each molecule. The successive stacking of the PGRP-LE molecule forms an infinitely long oligomer in the crystal and is shown in the inset. A repeating dimeric unit composed of two molecules each of PGRP-LE and TCT is highlighted.

Figure 5.
FIGURE 5. Activation of the PGRP-LC/IMD pathway by polymeric DAP-type PGN. a, the four ends of TCT bound to the first molecule of PGRP-LE are not blocked. The C1 hydroxyl group of MurNAc was modeled in the configuration. The entrances for a -(1,4)-glycosidic bond at both hydroxyl groups (C4 position of GlcNAc and C1 position of MurNAc) are not blocked by any neighboring residue of PGRP-LE and -LCx. Bottom, entrances for peptide cross-link are also opened. b, a model of clustering of PGRP-LCx on polymeric PGN. A layer of DAP-type PGN was modeled. In this model, every second and fifth stem peptide from a glycan chain is cross-linked to a stem peptide from a different glycan chain, reflecting the degreeofcross-linkinginE. coliPGN. Due to steric hindrance, if one PGRP-LCx molecule binds to an arbitrarily first monomeric PGN unit, another molecule binds the fifth or a farther monomeric unit on a glycan chain. An orthogonal view of the model shows a schematic diagram of the juxtaposition of the cytoplasmic domains, triggering the IMD pathway signaling.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 8286-8295) copyright 2006.

Figures were selected by an automated process.