PMID:23326499

Citation	Sharma, P, Dube, D, Sinha, M, Yadav, S, Kaur, P, Sharma, S and Singh, TP (2013) Structural insights into the dual strategy of recognition by peptidoglycan recognition protein, PGRP-S: structure of the ternary complex of PGRP-S with lipopolysaccharide and stearic acid. PLoS ONE 8:e53756
Abstract	Peptidoglycan recognition proteins (PGRPs) are part of the innate immune system. The 19 kDa Short PGRP (PGRP-S) is one of the four mammalian PGRPs. The concentration of PGRP-S in camel (CPGRP-S) has been shown to increase considerably during mastitis. The structure of CPGRP-S consists of four protein molecules designated as A, B, C and D forming stable intermolecular contacts, A-B and C-D. The A-B and C-D interfaces are located on the opposite sides of the same monomer leading to the the formation of a linear chain with alternating A-B and C-D contacts. Two ligand binding sites, one at C-D contact and another at A-B contact have been observed. CPGRP-S binds to the components of bacterial cell wall molecules such as lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN) from both gram-positive and gram-negative bacteria. It also binds to fatty acids including mycolic acid of the Mycobacterium tuberculosis (Mtb). Previous structural studies of binary complexes of CPGRP-S with LPS and stearic acid (SA) have shown that LPS binds to CPGRP-S at C-D contact (Site-1) while SA binds to it at the A-B contact (Site-2). The binding studies using surface plasmon resonance showed that LPS and SA bound to CPGRP-S in the presence of each other. The structure determination of the ternary complex showed that LPS and SA bound to CPGRP-S at Site-1 and Site-2 respectively. LPS formed 13 hydrogen bonds and 159 van der Waals contacts (distances ≤4.2 Å) while SA formed 56 van der Waals contacts. The ELISA test showed that increased levels of productions of pro-inflammatory cytokines TNF-α and IFN-γ due to LPS and SA decreased considerably upon the addition of CPGRP-S.
Links	PubMed PMC3541179 Online version:10.1371/journal.pone.0053756
Keywords	Animals; Binding Sites; Camels; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Crystallography, X-Ray; Humans; Hydrogen Bonding; Ligands; Lipopolysaccharides/chemistry; Mycobacterium tuberculosis/chemistry; Mycolic Acids/chemistry; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Stearic Acids/chemistry; Ternary Complex Factors/chemistry
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CAMDR:PGRP1		GO:0001818: negative regulation of cytokine production	ECO:0000314:		P		Figure 3	complete CACAO 9540
CAMDR:PGRP1		GO:1900016: negative regulation of cytokine production involved in inflammatory response	ECO:0000314:		P		Figure 3	complete CACAO 9582
CAMDR:PGRP1	involved_in	GO:0001818: negative regulation of cytokine production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.