Structural basis for peptidoglycan binding by peptidoglycan recognition proteins

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-Å resolution, of the C-terminal PGN-binding domain of human PGRP-Iα in complex with a muramyl tripeptide representing the core of lysine-type PGNs from Gram-positive bacteria. 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 can accommodate a linked N-acetylglucosamine. Although most interactions are with the peptide, the glycan moiety also seems to be essential for specific recognition by PGRPs. Conservation of key PGN-contacting residues shows that all PGRPs employ this basic PGN-binding mode. The structure pinpoints variable residues that likely mediate discrimination between lysine- and diaminopimelic acid-type PGNs. We also propose a mechanism for PGN hydrolysis by Zn2+-containing PGRPs.

Original languageEnglish
Pages (from-to)17168-17173
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number49
DOIs
Publication statusPublished - 7 Dec 2004
Externally publishedYes

Keywords

  • Bacteria
  • Complex
  • Crystal structure
  • Innate immunity
  • Receptor

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