Structural Basis of Recognition of Pathogen-associated Molecular Patterns and Inhibition of Proinflammatory Cytokines by Camel Peptidoglycan Recognition Protein

Sharma, Pradeep; Dube, Divya; Singh, Amar; Mishra, Biswajit; Singh, Nagendra; Sinha, Mau; Dey, Sharmistha; Kaur, Punit; Mitra, Dipendra Kumar; Sharma, Sujata; Singh, T.P.

doi:10.1074/jbc.m111.228163

Cited by 36 publications

(42 citation statements)

References 28 publications

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“…These steps further reduced the values of R cryst factors to 25.3 and 27.8% for structures GlcNAc and MurNAc, respectively. The Fourier (2 F o Ϫ F c ) and difference Fourier (F o Ϫ F c ) maps computed at this stage showed the presence of significant non-protein electron densities at the ligand binding cleft in molecule C. It may be recalled that the ligand binding site in CPGRP-S is located in molecule C at the C-D contact (4,5). The ligands GlcNAc and MurNAc were fitted well into the electron densities (Fig.…”

Section: Methodsmentioning

confidence: 93%

Structural Studies on Molecular Interactions between Camel Peptidoglycan Recognition Protein, CPGRP-S, and Peptidoglycan Moieties N-Acetylglucosamine and N-Acetylmuramic Acid

Sharma

Yamini

Dube

et al. 2012

Journal of Biological Chemistry

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Background: PGRP-S is an innate immunity protein that protects hosts from invading microbes. Results: CPGRP-S forms linear polymers with alternating A-B and C-D contacts, and both GlcNAc and MurNAc bind at the same subsite. Conclusion:The mode of binding of camel PGRP-S is different from other PGRPs. Significance: The better antibacterial properties of camel PGRP-S can be exploited for therapeutic applications.

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Section: Methodsmentioning

confidence: 93%

Structural Studies on Molecular Interactions between Camel Peptidoglycan Recognition Protein, CPGRP-S, and Peptidoglycan Moieties N-Acetylglucosamine and N-Acetylmuramic Acid

Sharma

Yamini

Dube

et al. 2012

Journal of Biological Chemistry

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“…The PGRP concentration in camel milk is 370 mg/L and its expression was seen constant during the lactation period [10,19]. The antiinflammatory activity of the camel PGRP was demonstrated in mice model intoxicated with LPS or LTA by inhibition of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) and the dramatic reduction in the mortality rate [20].…”

Section: Peptidoglycan Recognition Protein (Pgrp)mentioning

confidence: 99%

“…The PGRP is pattern recognition receptor (PRR) that plays important role in preventing the adhesion and bacterial multiplication through the attachment to the lipopolysaccharides (LPS) and lipoteichoic acid (LTA) of Gram-negative and the Gram-positive bacteria, respectively [20]. The PGRP is an important bacterial inhibitory protein that present in high concentration in camel milk and has the MW of 19.11 KD and its cDNA full sequence is 700 bp.…”

Section: Peptidoglycan Recognition Protein (Pgrp)mentioning

confidence: 99%

The Camel's (Camelus Dromedarius) Mammary Gland Immune System in Health and Disease

Alluwaimi¹,

Salem²,

Al-Ashqer³

et al. 2017

J Adv Dairy Res

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Dromedary camel (Camelus dromedarius) can survive and produce considerable amount of milk during recurrent and prolonged hot and dry environment. Camel milk considered one of the most valuable food sources due to its nutritional value. Intramammary infection and other low hygienic measurers are the main factors that undermined the camel mammary gland welfare. Available studies elaborated in detail the role of innate factors like Peptidoglycan recognition protein and Lactoferrin in camel milk as potent antimicrobial factors. Despite the wide studies on camel antibodies, their role in the mammary gland immunity was scarcely addressed. The major lack of information about the immune system of camel mammary gland is of great setback in improving the camel dairy industry. This review has evaluated the available data on different aspects of the mammary immune system. The available data unfortunately are of general profile, which created wide gaps in understanding the camel mammary gland immune system in health and disease. Several measures were proposed as necessary approaches to drive considerable interests of wide and in depth research on the camel mammary gland immune system.In conclusion, the available knowledge on the immune system of camel mammary gland suffers from major lack in the role of the immunoglobulins in health and mastitis. Although, acceptable progress was made on defining the cellular populations of the mammary gland, their main activity during the infection needs to be revealed.

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“…To establish the wide range of specificities of the binding site in tetrameric CPGRP-S for various PAMPs, we have determined two crystal structures of CPGRP-S complexed with (i) a single compound muramyl dipeptide (MDP), which is a moiety of PGN and (ii) two compounds GlcNAc and ␤-maltose. Previously, it has been shown that the PAMP-binding site in CPGRP-S was capable of recognizing both Gram-negative and -positive bacteria through its binding to LPS and LTA with equally high affinities (14). From the structure analysis of native CPGRP-S and its complexes with LPS and LTA, it was shown that multiple binding subsites were available for the recognition of PAMPs in the ligand binding site in the CPGRP-S tetramer.…”

mentioning

confidence: 99%

Multiligand Specificity of Pathogen-associated Molecular Pattern-binding Site in Peptidoglycan Recognition Protein

Sharma

Dube

Sinha

et al. 2011

Journal of Biological Chemistry

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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 Å resolution and (ii) GlcNAc and ␤-maltose at 1.7Å 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 Peptidoglycan recognition proteins (PGRPs) 2 of the innate immune system provide the first line of defense to hosts against infecting microbes. These proteins specifically recognize pathogen-associated molecular patterns (PAMPs) such as peptidoglycan (PGN), LPS, lipoteichoic acid (LTA), mycolic acid, and etc. It is well known that PGN is present on the cell walls of both Gram-negative and -positive bacteria. PGN is a polymer of alternating GlcNAc and N-acetylmuramic acid (MurNAc) in a ␤(134) linkage, cross-linked by short peptide stems composed of alternating L-and D-amino acids. The glycan moiety of PGN is conserved among almost all of the bacteria, but the peptide part displays a considerable diversity (1). According to the amino acid residue at number three position of the peptide stem, PGNs are divided into two major categories, (i) lysine type (Lys-type) and (ii) meso-diaminopimelic acid type. The peptidoglycans or their fragments are recognized by the host through innate immunity proteins, particularly PGRPs (2).PGRPs are highly conserved molecules (3-7), which bind to PGN and other PAMPs as well as to their fragments and derivatives with varying affinities (8). There are four types of mammalian PGRPs designated as short PGRP (PGRP-S), PGRP-L, PGRP-I␣, and PGRP-I␤ representing short (molecular mass, 20 -25 kDa), long (molecular mass, up to 90 kDa), and intermediate (molecular mass, 40 -45 kDa), respectively. PGRP-S contains ϳ200 amino acid residues and represents a single PGRP domain, wheraes PGRP-L and PGRP-I also contain a similar C-terminal PGRP domain. PGRP-S shows direct bacterial recognition. The potency of its recognition determines its strength in controlling bacterial infections. Initially, PGRP-S was detected in bone marrow (6), whereas subsequently, it was also observed as a soluble protein in the granules of polymorphonuclear leukocytes (9). This observation implied that PGRP-S might have a role as an antibacterial agent (6). Recently, its presence has also been shown in milk of certain species of mammals (10) and in the intestinal M cells (11). As far as mammary gland secretions are concerned, so far, PGRP-S has been detected in the mammary secretions of porcine and camel only (10). As far as structural studies are concerned, the crystal structures of truncated human PGRP-S (HPGRP-S) (amino acid residues from 9 to 191) and a full-length (amino acid residues from 1 to 171) camel PGRP-S (CPGRP-S) have been reported (12,13) showing truncated HPGRP-S as a monom...

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Structural Basis of Recognition of Pathogen-associated Molecular Patterns and Inhibition of Proinflammatory Cytokines by Camel Peptidoglycan Recognition Protein

Cited by 36 publications

References 28 publications

Structural Studies on Molecular Interactions between Camel Peptidoglycan Recognition Protein, CPGRP-S, and Peptidoglycan Moieties N-Acetylglucosamine and N-Acetylmuramic Acid

Structural Studies on Molecular Interactions between Camel Peptidoglycan Recognition Protein, CPGRP-S, and Peptidoglycan Moieties N-Acetylglucosamine and N-Acetylmuramic Acid

The Camel's (Camelus Dromedarius) Mammary Gland Immune System in Health and Disease

Multiligand Specificity of Pathogen-associated Molecular Pattern-binding Site in Peptidoglycan Recognition Protein

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