Structural Basis for Peptidoglycan Binding by Peptidoglycan Recognition Proteins

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Dec 2

PMID 15572450

Citations 56

Authors

Rongjin Guan

Abhijit Roychowdhury

Brian Ember

Sanjay Kumar

Geert-Jan Boons

Roy A Mariuzza

Affiliations

Soon will be listed here.

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-A resolution, of the C-terminal PGN-binding domain of human PGRP-Ialpha 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 Zn(2+)-containing PGRPs.

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