Long pentraxins: an emerging group of proteins with diverse functions

Goodman, Adam R.; Cardozo, Timothy; Abagyan, Ruben; Altmeyer, Anne; Wisniewski, Hans‐Georg; Vilček, Ján

doi:10.1016/1359-6101(96)00019-6

Cited by 130 publications

(126 citation statements)

References 54 publications

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“…PTX3 belongs to the subfamily of long pentraxins with a C-terminal 203 amino-acid sequence comparable to the short pentraxins (eg C-reactive protein) and an Nterminal 178 amino-acid unrelated portion (Breviario et al, 1992;Goodman et al, 1996;Bottazzi et al, 1997). The exact function of PTX3 remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major Depression

Shelton

Shan

Peng

et al. 2003

Neuropsychopharmacol

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In this study, differential display technology was used to compare gene expression in cultured fibroblasts from patients with major depression, melancholic subtype vs nonmelancholic depressives and normal volunteer controls. Genes differentially expressed in depressives and normals included an overexpressed 269 bp sequence tag showing B95% identity with the Homo sapiens long pentraxin 3 (PTX3) gene sequence in the 3 0 noncoding region. The 269 bp complimentary DNA probe hybridized with the 1.9 kb PTX3 mRNA. The densitometric analysis of slot blots showed that the mean steady-state mRNA level of PTX3 was 3.5-fold higher in the melancholic group as compared to that in normal controls and in nonmelancholic depressives (n ¼ 8, all groups). Incubation experiments were then conducted: confluent fibroblasts from melancholics and normal volunteers were incubated with isoproterenol 1 mM, dexamethasone (DEX) 500 nM, and interleukin 1b (IL-1b) 50 ng/ml, for 0, 0.5, 1, 4, and 24 h. mRNA was isolated and quantitated using Northern blot analysis. Isoproterenol produced no significant change in PTX3 expression; DEX produced a significant increase at 4 and 24 h; IL-1b induced an increase in both the groups that peaked at 4 h, declining to near basal levels at 24 h. There were no differences between melancholics or controls in mean change or maximum response with either DEX or IL-1b. The results are consistent with the reported effects of IL-1b on PTX3 expression in mouse brain. The results are of potential importance because PTX3 is a member of the long pentraxin subfamily of acute-phase proteins, which is inducible by IL-1b, and may play roles in neuroimmunity and neuroprotection.

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Section: Introductionmentioning

confidence: 99%

Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major Depression

Shelton

Shan

Peng

et al. 2003

Neuropsychopharmacol

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“…The mature protein contains nine cysteine residues: three are located within the N-terminal region (Cys 47 , Cys 49 , and Cys 103 ), and six are in the C-terminal domain (Cys 179 , Cys 210 , Cys 271 , Cys 317 , Cys 318 , and Cys 357 ). Cys residues at positions 210 and 271 are highly conserved among pentraxins and based on the homology with CRP and SAP are predicted to be engaged in an intrachain disulfide bond (22,23).…”

mentioning

confidence: 99%

“…Like other members of the long pentraxin subfamily, human PTX3 is composed of a pentraxin-like C-terminal domain (amino acids 179 -381), which is homologous to the entire short pentraxin amino acid sequence, and an unrelated N-terminal region (amino acids 18 -178) (22,23). The human protein has a unique N-glycosylation site at Asn 220 that has been described to be fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary sugars (24).…”

mentioning

confidence: 99%

Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization

Inforzato

Rivieccio²,

Morreale

et al. 2008

Journal of Biological Chemistry

123

129

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PTX3 is an acute phase glycoprotein that plays key roles in resistance to certain pathogens and in female fertility. PTX3 exerts its functions by interacting with a number of structurally unrelated molecules, a capacity that is likely to rely on its complex multimeric structure stabilized by interchain disulfide bonds. In this study, PAGE analyses performed under both native and denaturing conditions indicated that human recombinant PTX3 is mainly composed of covalently linked octamers. The network of disulfide bonds supporting this octameric assembly was resolved by mass spectrometry and Cys to Ser site-directed mutagenesis. Here we report that cysteine residues at positions 47, 49, and 103 in the N-terminal domain form three symmetric interchain disulfide bonds stabilizing four protein subunits in a tetrameric arrangement. Additional interchain disulfide bonds formed by the C-terminal domain cysteines Cys 317 and Cys 318 are responsible for linking the PTX3 tetramers into octamers. We also identified three intrachain disulfide bonds within the C-terminal domain that we used as structural constraints to build a new three-dimensional model for this domain. Previously it has been shown that PTX3 is a key component of the cumulus oophorus extracellular matrix, which forms around the oocyte prior to ovulation, because cumuli from PTX3 ؊/؊ mice show defective matrix organization. Recombinant PTX3 is able to restore the normal phenotype ex vivo in cumuli from PTX3 ؊/؊ mice. Here we demonstrate that PTX3 Cys to Ser mutants, mainly assembled into tetramers, exhibited wild type rescue activity, whereas a mutant, predominantly composed of dimers, had impaired functionality. These findings indicate that protein oligomerization is essential for PTX3 activity within the cumulus matrix and implicate PTX3 tetramers as the functional molecular units required for cumulus matrix organization and stabilization.

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“…Furthermore, rats display considerable luminal shedding of senescent colonocytes, whereas in humans mucosal phagocytosis is the main route of colonocyte disposal [39]. Especially, the latter observation may be of high relevance if Mptx indeed has a role in recognition, binding and clearance of apoptotic (dead) cells, similar to SAP and CRP [9,11,15,17,20]. The question is how this difference between man and rodents will affect extrapolation of dietary exposure and other studies in these animals.…”

Section: Discussionmentioning

confidence: 99%

“…Reduced levels lead to autoimmune disease [2,26,29,30]. More specifically, they are thought to be involved in the recognition, binding and clearance of dead and apoptotic cells or cellular debris of pathogenic cells and host cells [9,11,15,17,20].…”

Section: Introductionmentioning

confidence: 99%

Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans

et al. 2007

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Mucosal pentraxin (Mptx), identified in rats, is a short pentraxin of unknown function. Other subfamily members are Serum amyloid P component (SAP), Creactive protein (CRP) and Jeltraxin. Rat Mptx mRNA is predominantly expressed in colon and in vivo is strongly (30-fold) regulated by dietary heme and calcium, modulators of colon cancer risk. This renders Mptx a potential nutrient sensitive biomarker of gut health. To support a role as biomarker, we examined whether the pentraxin protein structure is conserved, whether Mptx protein is nutrientsensitively expressed and whether Mptx is expressed in mouse and human. Sequence comparison and 3D modelling showed that rat Mptx is highly homologous to the other pentraxins. The calcium-binding site and subunit interaction sites are highly conserved, while a loop deletion and charged residues contribute to a distinctive ''top'' face of the pentamer. In accordance with mRNA expression, Mptx protein is strongly down-regulated in rat colon mucosa in response to high dietary heme intake. Mptx mRNA is expressed in rat and mouse colon, but not in human colon. A stop codon at the beginning of human exon two indicates loss of function, which may be related to differences in intestinal cell turnover between man and rodents.

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Long pentraxins: an emerging group of proteins with diverse functions

Cited by 130 publications

References 54 publications

Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major Depression

Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major Depression

Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization

Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans

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