Crystal structure of peptidoglycan recognition protein LB from Drosophila melanogaster

Abstract

The family of peptidoglycan recognition proteins (PGRPs) are associated with the recognition of the peptidoglycan of microbes and subsequent activation of signaling pathways for immune response. Here the crystal structure of Drosophila PGRP-LB is determined at a resolution of 2.0 A and shows an active-site cleft with a zinc cage. Poor conservation of surface residues at the cleft predicts a widely varying individual specificity of PGRPs for molecular patterns on microbial cell walls. At the back of this cleft is a putatively conserved distinctive groove. The location and mainly hydrophobic nature of the groove indicate that the back face serves for subsequent signaling after clustering of PGRP molecules by binding to polymeric cell wall components.

Peptidoglycan Recognition Proteins Involved in 1,3-β-D-Glucan-dependent Prophenoloxidase Activation System of Insect

“…Also, it was reported that Drosophila Toll was activated by Gram-negative bacteria through a circulating PGRP-SA molecule (44). The crystal structure of Drosophila PGRP-LB demonstrates that poor conservation of surface residues at the active sites predicts a widely varying individual specificity of PGRPs for molecular patterns on microbial cell walls (45). Further these data suggest that the PGRP family has a principal role in sensing pathogens and that distinct PGRP molecules recognize different classes of microorganisms.…”

Peptidoglycan recognition proteins (PGRPs)

“…The crystal structures of PGRPs reveal a general design similar to type 2 bacteriophage amidases: they all have three peripheral ␣ helices and several central ␤-sheet strands ( Figure 3) [7,[10][11][12][13]. The front face of the molecule has a cleft that forms a peptidoglycan-binding groove ( Figure 3), and the back of the molecule has a PGRP-specific segment (not present in bacteriophage amidases), which is often hydrophobic and is also …”

“…Crystallographic analysis of human PGLYRP-1 and the carboxy-terminal PGRP domain of PGLYRP-3, as well as insect PGRP-LB, -SA, -LC and -LE, show that all these PGRPs have a ligand-binding groove that binds peptidoglycan and is specific for MurNAc bound to three peptide-bonded amino acids (muramyl-tripeptide), which is the minimum peptidoglycan fragment hydrolyzed by PGLYRP-2 [7,9,[10][11][12][13][52][53][54][55]. It can accommodate a larger structure, such as GlcNAcMurNAc-tetrapeptide or MurNAc-pentapeptide (Figure 3), but it does not bind muramyl-dipeptide or a peptide without MurNAc [56][57][58].…”

Molecular cloning and functional characterization of peptidoglycan recognition protein 6 in grass carp Ctenopharyngodon idella

“…The activation of insect PGRPs by Gram-positive or Gram-negative bacteria may trigger Toll (Gobert et al, 2003) and immune deficiency (Imd) signal transduction pathways (Takehana et al, 2002) and the prophenol-oxidase cascade (Takehana et al, 2002), which results in the production of antimicrobial effectors. In addition, some insect PGRPs such as Drosophila PGRP-SC1 and PGRP-LB are N-acetylmuramoyl-L-alanine amidases (Kim et al, 2003;Mellroth et al, 2003), which can hydrolyze proinflammatory peptidoglycans. One insect PGRP, Drosophila PGRP-SA, which is not an amidase, has an L,D-carboxypeptidase activity for diaminopimelic acid-type tetrapeptide peptidoglycan fragments (Chang et al, 2004).…”