Publication Abstract from PubMed
The peptidoglycan recognition protein PGRP-S is an innate immunity molecule that specifically interacts with microbial peptidoglycans and other pathogen-associated molecular patterns. We report here two structures of the unique tetrameric camel PGRP-S (CPGRP-S) complexed with (i) muramyl dipeptide (MDP) at 2.5 A resolution and (ii) GlcNAc and beta-maltose at 1.7A resolution. The binding studies carried out using surface plasmon resonance indicated that CPGRP-S binds to MDP with a dissociation constant of 10(-7) M, whereas the binding affinities for GlcNAc and beta-maltose separately are in the range of 10(-4) M to 10(-5) M, whereas the dissociation constant for the mixture of GlcNAc and maltose was estimated to be 10(-6) M. The data from bacterial suspension culture experiments showed a significant inhibition of the growth of Staphylococcus aureus cells when CPGRP-S was added to culture medium. The ELISA experiment showed that the amount of MDP-induced production of TNF-alpha and IL-6 decreased considerably after the introduction of CPGRP-S. The crystal structure determinations of (i) a binary complex with MDP and (ii) a ternary complex with GlcNAc and beta-maltose revealed that MDP, GlcNAc, and beta-maltose bound to CPGRP-S in the ligand binding cleft, which is situated at the interface of molecules C and D of the homotetramer formed by four protein molecules A, B, C, and D. In the binary complex, the muramyl moiety of MDP is observed at the C-D interface, whereas the peptide chain protrudes into the center of tetramer. In the ternary complex, GlcNAc and beta-maltose occupy distinct non-overlapping positions belonging to different subsites.
Multiligand specificity of pathogen-associated molecular pattern-binding site in peptidoglycan recognition protein.,Sharma P, Dube D, Sinha M, Mishra B, Dey S, Mal G, Pathak KM, Kaur P, Sharma S, Singh TP J Biol Chem. 2011 Sep 9;286(36):31723-30. Epub 2011 Jul 22. PMID:21784863[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
