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.
journal_name
Proc Natl Acad Sci U S Aauthors
Guan R,Roychowdhury A,Ember B,Kumar S,Boons GJ,Mariuzza RAdoi
10.1073/pnas.0407856101keywords:
subject
Has Abstractpub_date
2004-12-07 00:00:00pages
17168-73issue
49eissn
0027-8424issn
1091-6490pii
0407856101journal_volume
101pub_type
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