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

Sharma, Pradeep; Yamini, S.; Dube, Divya; Singh, Amar; Sinha, Mau; Dey, Sharmistha; Mitra, Dipendra Kumar; Kaur, Punit; Sharma, Sujata

doi:10.1074/jbc.m111.321307

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…The observed forcep-like shape of the cleft formed by two α-helices Aα2 and Bα2 at the A–B contact provides features similar as that observed in the case of other fatty acid binding proteins [21], [22]. On the other hand the cleft at the C–D contact consists of a specific pocket for the recognition of glycan moieties such as GlcNAc and MurNAc [11]. In a contrast, it was shown in the structures of the complexes of PGRP-S domain of HPGRP-Iα and HPGRP-Iβ, that the peptide moiety of PGN was the initial element of recognition by the protein [23], [24].…”

Section: Discussionsupporting

confidence: 75%

“…It has been shown by previous structural studies of binary complexes of CPGRP-S with LPS and SA [9]–[11] that LPS bound to CPGRP-S in the binding Site-1 at the C–D contact while SA was found to bind the protein in the binding Site-2 at the A–B contact [19]. Since the two binding sites were located distantly from each other, the surface plasmon resonance studies were carried out with both ligands separately as well as one after the other.…”

Section: Resultsmentioning

confidence: 84%

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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

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 75%

Section: Resultsmentioning

confidence: 84%

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

et al. 2013

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“…It is possible that the free Cys was not on the molecule surface; however, no structure is known to date. A second affinity constant for PGRP–PGN interaction was determined, suggesting a cooperative binding effect that would be caused by PGRP aggregation or binding of multiple PGRP molecules to each PGN molecule . In this sense, PGRP dimerization could have a physiological role in PGN recognition.…”

Section: Discussionmentioning

confidence: 95%

“…The hydrophobic nature of the PGRP‐LB groove indicates that the back face would serve for subsequent signalling after PGRP molecule clustering by binding to polymeric cell wall components . Binding and crystallographic studies demonstrate that CPGRP‐S bind to lipopolysaccharide and PGN …”

Section: Introductionmentioning

confidence: 99%

Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response

et al. 2015

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SummaryPeptidoglycan recognition proteins (PGRP) are pattern recognition receptors that can bind or hydrolyse peptidoglycan (PGN). Four human PGRP have been described: PGRP-S, PGRP-L, PGRP-Ia and PGRP-Ib. Mammalian PGRP-S has been implicated in intracellular destruction of bacteria by polymorphonuclear cells, PGRP-Ia and PGRP-Ib have been found in keratinocytes and epithelial cells, and PGRP-L is a serum protein that hydrolyses PGN. We have expressed recombinant human PGRP and observed that PGRP-S and PGRP-Ia exist as monomer and disulphide dimer proteins. The PGRP dimers maintain their biological functions. We detected the PGRP-S dimer in human serum and polymorphonuclear cells, from where it is secreted after degranulation; these cells being a possible source of serum PGRP-S. Recombinant PGRP do not act as bactericidal or bacteriostatic agents in the assayed conditions; however, PGRP-S and PGRP-Ia cause slight damage in the bacterial membrane. Monocytes/ macrophages increase Staphylococcus aureus phagocytosis in the presence of PGRP-S, PGRP-Ia and PGRP-Ib. All PGRP bind to monocyte/macrophage membranes and are endocytosed by them. In addition, all PGRP protect cells from PGN-induced apoptosis. PGRP increase THP-1 cell proliferation and enhance activation by PGN. PGRP-S-PGN complexes increase the membrane expression of CD14, CD80 and CD86, and enhance secretion of interleukin-8, interleukin-12 and tumour necrosis factor-a, but reduce interleukin-10, clearly inducing an inflammatory profile.

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“…Docking of N-acetylmuramic acid (NAM) with Rv3717 was performed using the PatchDock server (Schneidman-Duhovny et al, 2005). Coordinates of NAM were obtained from the complex structure of the peptidoglycan-recognition protein in complex with NAM (PDB entry 3olk; Sharma et al, 2012). All parameters used for docking were the defaults of the PatchDock server.…”

Section: Docking Of Substrate With Rv3717mentioning

confidence: 99%

The structure of Rv3717 reveals a novel amidase fromMycobacterium tuberculosis

Kumar

et al. 2013

Acta Crystallogr D Biol Cryst

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The structure of Rv3717 determined to 1.7 Å resolution by Pt-SAD phasing reveals a unique autolysin that lacks a cell-wall-binding domain. Rv3717 utilizes its net positive charge for substrate binding and exhibits activity towards a broad spectrum of substrate cell walls. Structural analysis reveals that Rv3717 utilizes a β-hairpin turn at its N-terminus to autoregulate its enzymatic activity.

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

Cited by 6 publications

References 39 publications

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

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

Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response

The structure of Rv3717 reveals a novel amidase fromMycobacterium tuberculosis

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