This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Guan, R. Articles by Mariuzza, R. A. Search for Related Content PubMed PubMed Citation Articles by Guan, R. Articles by Mariuzza, R. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLYCINE Social Bookmarking                         What's this?

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

Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, Maryland, USA

Abhijit Roychowdury

Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA

Brian Ember

Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA

Sanjay Kumar

Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA

Geert-Jan Boons

Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA

Roy A. Mariuzza

Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, Maryland, USA, mariuzza{at}carb.nist.gov

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-I 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.

Key Words: Innate immunity • peptidogylcan • PGRP • receptor • crystal structure

Journal of Endotoxin Research, Vol. 11, No. 1, 41-46 (2005)
DOI: 10.1177/09680519050110010901


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?