4gf9 | pdb_00004gf9
Structural insights into the dual strategy of recognition of peptidoglycan recognition protein, PGRP-S: ternary complex of PGRP-S with LPS and fatty acid
Structural highlights
FunctionPGRP1_CAMDR Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Binds also to Gram-negative bacteria. Involved in innate immunity. Is microbicidal for Gram-positive and Gram-negative bacteria and yeast. May function in intracellular killing of bacteria (By similarity). Publication Abstract from PubMedPeptidoglycan 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 A) while SA formed 56 van der Waals contacts. The ELISA test showed that increased levels of productions of pro-inflammatory cytokines TNF-alpha and IFN-gamma due to LPS and SA decreased considerably upon the addition of CPGRP-S. 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.,Sharma P, Dube D, Sinha M, Yadav S, Kaur P, Sharma S, Singh TP PLoS One. 2013;8(1):e53756. doi: 10.1371/journal.pone.0053756. Epub 2013 Jan 9. PMID:23326499[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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