1S2J

Crystal structure of the Drosophila pattern-recognition receptor PGRP-SA

Summary for 1S2J

• Entry DOI: 10.2210/pdb1s2j/pdb
• Descriptor: Peptidoglycan recognition protein SA CG11709-PA, PHOSPHATE ION (3 entities in total)
• Functional Keywords: mixed beta-sheet, pi-helix (one turn), hydrolase
• Biological source: Drosophila melanogaster (fruit fly)
• Cellular location: Secreted: Q9VYX7
• Total number of polymer chains: 2
• Total formula weight: 46788.38

Authors

Chang, C.-I.,Pili-Floury, S.,Chelliah, Y.,Lemaitre, B.,Mengin-Lecreulx, D.,Deisenhofer, J. (deposition date: 2004-01-08, release date: 2004-09-14, Last modification date: 2023-08-23)

Primary citation

Chang, C.-I.,Pili-Floury, S.,Herve, M.,Parquet, C.,Chelliah, Y.,Lemaitre, B.,Mengin-Lecreulx, D.,Deisenhofer, J.
A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual l,d-carboxypeptidase activity.
PLOS BIOL., 2:1293-1302, 2004

PubMed 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-A 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 PGRP-SA 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 lysine-type 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.

PubMed: 15361936
DOI: 10.1371/journal.pbio.0020277

Experimental method

X-RAY DIFFRACTION (2.2 Å)