Crystal structure of a peptidoglycan recognition protein (PGRP) in complex with a muramyl tripeptide from Gram-positive bacteria

Rongjin Guan, Abhijit Roychowdury, Brian Ember, Sanjay Kumar, Geert Jan Boons*, Roy A. Mariuzza

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind, and in some cases hydrolyse, bacterial peptidoglycans (PGNs). We determined the crystal structure of the C-terminal PGN-binding domain of human PGRP-Iα in complex with a muramyl tripeptide representing the conserved core of lysine-type PGNs. The peptide stem of the ligand is buried at the deep end of a long binding groove, with N-acetylmuramic acid situated in the middle of the groove, whose shallow end could accommodate N-acetylglucosamine. Both peptide and glycan moieties are essential for binding by PGRPs. Conservation of key PGN-contacting residues indicates that all PGRPs employ this basic PGN-binding mode. The structure identifies variable residues that likely mediate discrimination between lysine- and diaminopimelic acid-type PGNS. In addition, we propose a mechanism for PGN hydrolysis by Zn2+-containing catalytic PGRPS.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalJournal of Endotoxin Research
Volume11
Issue number1
DOIs
Publication statusPublished - 29 Apr 2005
Externally publishedYes

Keywords

  • Crystal structure
  • Innate immunity
  • Peptidoglycan
  • PGRP
  • Receptor

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