Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.

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.

authors

Guan R,Roychowdhury A,Ember B,Kumar S,Boons GJ,Mariuzza RA

doi

10.1073/pnas.0407856101

keywords:

subject

Has Abstract

pub_date

2004-12-07 00:00:00

pages

17168-73

issue

49

eissn

0027-8424

issn

1091-6490

pii

0407856101

journal_volume

101

pub_type

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