Crystal structure of the Drosophila peptidoglycan recognition protein (PGRP)-SA at 1.56 A resolution

J Mol Biol. 2004 Jul 16;340(4):909-17. doi: 10.1016/j.jmb.2004.04.077.

Abstract

Peptidoglycan recognition proteins (PGRPs) form a recently discovered protein family, which is conserved from insect to mammals and is implicated in the innate immune system by interacting with/or degrading microbial peptidoglycans (PGNs). Drosophila PGRP-SA is a member of this family of pattern recognition receptors and is involved in insect Toll activation. We report here the crystal structure of PGRP-SA at 1.56 A resolution, which represents the first example of a "recognition" PGRP. Comparison with the catalytic Drosophila PGRP-LB reveals an overall structure conservation with an L-shaped hydrophilic groove that is likely the PGN carbohydrate core binding site, but further suggests some possible functional homology between recognition and catalytic PGRPs. Consistent with sequence analysis, PGRP-SA does not contain the canonical zinc-binding residues found in catalytic PGRPs. However, substitution of the zinc-binding cysteine residue by serine, along with an altered coordinating histidine residue, assembles a constellation of residues that resembles a modified catalytic triad. The serine/histidine juxtaposition to a threonine residue and a carbonyl oxygen atom, along with conservation of the catalytic water molecule found in PGRP-LB, tantalizingly suggests some hydrolytic function for this member of receptor PGRPs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Conserved Sequence
  • Crystallography, X-Ray*
  • Drosophila / chemistry*
  • Drosophila Proteins / chemistry*
  • Histidine / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Oxygen / chemistry
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • Serine / metabolism
  • Water / chemistry
  • X-Ray Diffraction

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • peptidoglycan recognition protein
  • Water
  • Serine
  • Histidine
  • Oxygen

Associated data

  • PDB/1SXR