title: Crystal structure of a peptidoglycan recognition protein (PGRP) in complex with a muramyl tripeptide from Gram-positive bacteria.
abstract: 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-Ialpha 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.
authors.affiliation: Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, Maryland, USA.
authors.forename: Rongjin
authors.initials: R
authors.lastname: Guan
authors.forename: Abhijit
authors.initials: A
authors.lastname: Roychowdury
authors.forename: Brian
authors.initials: B
authors.lastname: Ember
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
authors.forename: Roy A
authors.initials: RA
authors.lastname: Mariuzza
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D029721:Drosophila Proteins / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry; D006094:Gram-Positive Bacteria / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D002352:Carrier Proteins; D004220:Disulfides; D029721:Drosophila Proteins; D008024:Ligands; C118897:peptidoglycan recognition protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C035104:muramylNAc-Ala-isoGln-Lys-tripeptide; D005998:Glycine