A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity

Chung I. Chang, Sébastien Pili-Floury, Mireille Hervé, Claudine Parquet, Yogarany Chelliah, Bruno Lemaitre, Dominique Mengin-Lecreulx, Johann Deisenhofer

Research output: Contribution to journalArticle

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Abstract

The Drosophila peptidoglycan recognition protein SA (PGRP-SA) is critically involved in sensing bacterial infection and activating the Toll signaling pathway, which induces the expression of specific antimicrobial peptide genes. We have determined the crystal structure of PGRP-SA to 2.2-Å resolution and analyzed its peptidoglycan (PG) recognition and signaling activities. We found an extended surface groove in the structure of PGRP-SA, lined with residues that are highly diverse among different PGRPs. Mutational analysis identified it as a PG docking groove required for Toll signaling and showed that residue Ser158 is essential for both PG binding and Toll activation. Contrary to the general belief that PGRPSA has lost enzyme function and serves primarily for PG sensing, we found that it possesses an intrinsic L,D-carboxypeptidase activity for diaminopimelic acid-type tetrapeptide PG fragments but not lysinetype PG fragments, and that Ser158 and His42 may participate in the hydrolytic activity. As L,D-configured peptide bonds exist only in prokaryotes, this work reveals a rare enzymatic activity in a eukaryotic protein known for sensing bacteria and provides a possible explanation of how PGRP-SA mediates Toll activation specifically in response to lysine-type PG.

Original languageEnglish (US)
JournalPLoS Biology
Volume2
Issue number9
DOIs
StatePublished - Sep 2004

Fingerprint

carboxypeptidase D
Pattern Recognition Receptors
Peptidoglycan
peptidoglycans
Drosophila
receptors
Chemical activation
Diaminopimelic Acid
proteins
Peptides
carboxypeptidase L
Bacterial Infections
Lysine
Bacteria
Genes
Crystal structure
antimicrobial peptides

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity. / Chang, Chung I.; Pili-Floury, Sébastien; Hervé, Mireille; Parquet, Claudine; Chelliah, Yogarany; Lemaitre, Bruno; Mengin-Lecreulx, Dominique; Deisenhofer, Johann.

In: PLoS Biology, Vol. 2, No. 9, 09.2004.

Research output: Contribution to journalArticle

Chang, Chung I. ; Pili-Floury, Sébastien ; Hervé, Mireille ; Parquet, Claudine ; Chelliah, Yogarany ; Lemaitre, Bruno ; Mengin-Lecreulx, Dominique ; Deisenhofer, Johann. / A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity. In: PLoS Biology. 2004 ; Vol. 2, No. 9.
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