A 20 amino acid synthetic peptide of a region from the 55 kDa human TNF receptor inhibits cytolytic and binding activities of recombinant human tumour necrosis factor<i>in vitro</i>

Hwang, Chanseok; Gatanaga, Maki; Innins, Elizabeth K.; Yamamoto, Robert S.; Granger, Gale A.; Gatanaga, Tetsuya

doi:10.1098/rspb.1991.0096

Cited by 13 publications

(4 citation statements)

References 21 publications

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“…It might be caused by the different hydropathy profile between the two peptides, or by the special conformation contributed from different amino acid residues (F143, F144, V151 and S152). Our results were partly consistent with the finding of Lie and Hwang that residues 130-149, a region connecting CRD3 and CRD4, and residues 146-165 in CRD4 were involved in the binding of TNF-α to TNF-R1 [12,17].…”

Section: Discussionsupporting

confidence: 94%

A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α

Cao

Wang

et al. 2009

Inflammation

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Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine, which has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Proinflammatory effect of TNF-alpha is activated mainly through human TNF receptor-1 (TNF-R1). However, the role of the fourth cystein-rich domain (CRD4) of TNF-R1 extracellular portion in the interaction of TNF-alpha with TNF-R1 is still unclear. In the present study, binding activity of TNF-alpha to TNF-R1 and protein levels of IkappaB-alpha and nuclear transcription factor kappa B (NF-kappaB) p65 subunit in HeLa cells were measured using enzyme-linked immunosorbent assay (ELISA) and western-blot analysis. Pep 3 (LRENECVS) which was derived from the hydrophilic region of A1 module in CRD4 remarkably inhibited the binding of TNF-alpha to TNF-R1, and also reversed TNF-alpha-induced degradation of IkappaB-alpha and nuclear translocation of NF-kappaB p65 subunit in HeLa cells. Our results confirmed that the hydrophilic region of A1 module in CRD4 participated in the interaction of TNF-alpha with TNF-R1, and demonstrated the potential of small-molecule TNF-alpha extracellular inhibitors targeting at A1 module in CRD4 of TNF-R1 in suppressing proinflammatory effect of TNF-alpha.

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Section: Discussionsupporting

confidence: 94%

A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α

Cao

Wang

et al. 2009

Inflammation

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“…This particular domain of the receptor may play a role in TNF binding, although binding was not affected by its deletion (5,18,26). TNF appears to play a protective role in RSV infection in culture and in mice (29), and it is tempting to speculate that soluble G protein could function as a TNF antagonist.…”

mentioning

confidence: 99%

The Central Conserved Cystine Noose of the Attachment G Protein of Human Respiratory Syncytial Virus Is Not Required for Efficient Viral Infection In Vitro or In Vivo

Teng

Collins

2002

J Virol

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The G glycoprotein of human respiratory syncytial virus (RSV) was identified previously as the viral attachment protein. Although we and others recently showed that G is not essential for replication in vitro, it does affect the efficiency of replication in a cell type-dependent fashion and is required for efficient replication in vivo. The ectodomain of G is composed of two heavily glycosylated domains with mucin-like characteristics that are separated by a short central region that is relatively devoid of glycosylation sites. This central region contains a 13-amino acid segment that is conserved in the same form among RSV isolates and is overlapped by a second segment containing four cysteine residues whose spacings are conserved in the same form and which create a cystine noose. The conserved nature of the cystine noose and flanking 13-amino acid segment suggested that this region likely was important for attachment activity. To test this hypothesis, we constructed recombinant RSVs from which the region containing the cysteine residues was deleted together with part or all of the conserved 13-amino acid segment. Surprisingly, each deletion had little or no effect on the intracellular synthesis and processing of the G protein, the kinetics or efficiency of virus replication in vitro, or sensitivity to neutralization by soluble heparin in vitro. In addition, neither deletion had any discernible effect on the ability of RSV to infect the upper respiratory tract of mice and both resulted in a 3-to 10-fold reduction in the lower respiratory tract. Thus, although the G protein is necessary for efficient virus replication in vivo, this activity does not require the central conserved cystine noose region.Human respiratory syncytial virus (RSV), the prototype of the Pneumovirus genus in the paramyxovirus family, is the most important viral etiologic agent of pediatric respiratory disease worldwide (6). Its genome consists of a single, negative-sense RNA of 15,190 to 15,225 nucleotides (for the three strains sequenced to date) encoding 10 major subgenomic mRNAs and 11 viral proteins. Three of these proteins, G, F, and SH, are transmembrane virion glycoproteins. The G glycoprotein has been identified as the viral attachment protein (25) although, as described below, under certain conditions it is completely dispensable for efficient replication in vitro. The F protein mediates membrane fusion and also appears to be able to serve as an auxiliary attachment protein (17,21,22,34,36). Expression of the SH protein can be eliminated with little effect on virus replication in vitro and in vivo and its function remains unknown (3, 41), although its counterpart in simian virus 5 was recently shown to function as an antagonist of apoptosis (16).RSV G is a highly glycosylated type II transmembrane protein with a single hydrophobic region near the N terminus which serves as both signal sequence and membrane anchor. The protein backbone is 292 to 299 amino acids long, depending on the virus strain (19,33), and has an M r of approxim...

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“…More recently, Howl and collaborators (17) also described the inhibitory properties of some synthetic peptides mimicking neurohypophysial hormone receptor. A 20-amino acid synthetic peptide derived from the tumor necrosis factor receptor inhibited the binding and the cytolytic activity of the corresponding recombinant human hormone (18). This approach has also been successfully used in characterizing hormonal receptor-G-protein interactions, such as synthetic peptides mimicking the third intracellular loop of the 5HT 1a receptor which prevent hormonal adenylyl cyclase inhibition (19), and also the interactions between other classes of proteins like actin-tropomyosin and calponin (20).…”

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confidence: 99%

Synthetic Rat V1a Vasopressin Receptor Fragments Interfere with Vasopressin Binding via Specific Interaction with the Receptor

Mendre¹,

Dufour²,

Roux³

et al. 1997

Journal of Biological Chemistry

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To study the vasopressin receptor domains involved in the hormonal binding, we synthesized natural and modified fragments of V 1a vasopressin receptor and tested their abilities to affect hormone-receptor interactions. Natural fragments mimicking the external loops one, two, and three were able to inhibit specific vasopressin binding to V 1a receptor. In contrast, the natural N-terminal part of the V 1a vasopressin receptor was found inactive. One fragment, derived from the external second loop and containing an additional C-terminal cysteine amide, was able to fully inhibit the specific binding of both labeled vasopressin agonist and antagonist to rat liver V 1a vasopressin receptor and the vasopressin-sensitive phospholipase C of WRK1 cells. The peptide-mediated inhibition involved specific interactions between the V 1a receptor and synthetic V 1a vasopressin receptor fragment since 1) it was dependent upon the vasopressin receptor subtype tested (K i(app) for the peptide: 3.7, 14.6, and 64.5 M for displacing [ 3 H]vasopressin from rat V 1a , V 1b , and V 2 receptors, respectively; 2) it was specific and did not affect sarcosin 1-angiotensin II binding to rat liver membranes; 3) it was not mimicked by vasopressin receptor unrelated peptides exhibiting putative detergent properties; and 4) no direct interaction between [ 3 H]vasopressin and synthetic peptide linked to an affinity chromatography column could be observed. Such an inhibition affected both the maximal binding capacity of the V 1a vasopressin receptor and its affinity for the labeled hormone, depending upon the dose of synthetic peptide used and was partially irreversible. Structure-activity studies using a serie of synthetic fragments revealed the importance of their size and cysteinyl composition. These data indicate that some peptides mimicking extracellular loops of the V 1a vasopressin receptor may interact with the vasopressin receptor itself and modify its coupling with phospholipase C.Vasopressin (AVP), 1 a small polypeptidic neurohypophysial hormone, exerts different biological effects in mammals. At the periphery, its major physiological role is played in regulating water and solute excretion by the kidney. This hormone is also involved in blood pressure control, platelet aggregation, corticotropin and aldosterone secretion (by the adenohypophysis and the adrenals, respectively), hepatic glycogenolysis, and uterine motility (for review, see Refs. 1 and 2). In the central nervous system, AVP is also involved in interneuronal communication (3). These distinct biological functions are mediated, in mammals, by at least three distinct receptor subtypes: V 2 , V 1a , and V 1b . V 2 receptors, involved in the antidiuretic response, are positively coupled to adenylyl cyclase (4). V 1a and V 1b receptors, involved in multiple peripheral responses and in corticotropin release, stimulate phospholipase C and activate protein kinase C (5, 6). Cloning the different subtypes of receptors (7-9) confirmed that these peptidic receptors belong to the family ...

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A 20 amino acid synthetic peptide of a region from the 55 kDa human TNF receptor inhibits cytolytic and binding activities of recombinant human tumour necrosis factorin vitro

Cited by 13 publications

References 21 publications

A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α

A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α

The Central Conserved Cystine Noose of the Attachment G Protein of Human Respiratory Syncytial Virus Is Not Required for Efficient Viral Infection In Vitro or In Vivo

Synthetic Rat V1a Vasopressin Receptor Fragments Interfere with Vasopressin Binding via Specific Interaction with the Receptor

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