Calcium-dependent polymerization of human serum amyloid P component is inhibited by heparin and dextran sulfate

Hamazaki, Hideaki

doi:10.1016/0167-4838(89)90279-3

Cited by 25 publications

(22 citation statements)

References 19 publications

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“…Proteins were radiolabeled with Na 125 I using IODO-BEADS TM as described (26). Protein concentrations were determined by absorbance at 280 nm using the following extinction coefficients: SAP, 18.2 (14); C4BP, 14.1 (18); and tentacles, 14.8, and core fragments, 12.5 (calculated as described by Perkins et al (28)). The molecular masses used in the calculations were 230 kDa for SAP, 570 kDa for C4BP, 48 kDa for the cleaved-off tentacles, and 160 kDa for the core fraction.…”

Section: Methodsmentioning

confidence: 99%

“…SAP has a high tendency to undergo calcium-dependent self-aggregation, which may be important for its deposition in amyloid. It has lectin-like properties and binds heparin, heparan and dermatan sulfate, and phosphorylethanolamine (13)(14)(15). Another property of SAP is its ability to bind DNA and chromatin (16).…”

Section: C4b-binding Protein (C4bp)mentioning

confidence: 99%

“…Inhibition of C4BP-SAP Interaction-SAP interacts with compounds such as phosphorylethanolamine and heparin (14,15). Their binding sites on the SAP molecule are probably related to the site that binds C4BP because heparin and phosphorylethanolamine have been shown to disrupt the C4BP-SAP interaction (4,15).…”

Section: Sap-sepharose Affinity Chromatography Of C4bp and Itsmentioning

confidence: 99%

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Serum Amyloid P Component Binding to C4b-binding Protein

Frutos¹,

Härdig

Dahlbäck

1995

Journal of Biological Chemistry

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Human C4b-binding protein (C4BP), which is a regulator of the classical complement pathway C3 convertase, forms high affinity complexes with anticoagulant protein S and with the pentraxin serum amyloid P component (SAP). SAP is a plasma protein present in all amyloid deposits. Recently, SAP was shown to inhibit the complement regulatory functions of C4BP. In this investigation, we have studied the structural requirements for the C4BP-SAP interaction. C4BP was subjected to chymotrypsin digestion, which yielded two major fragments corresponding to the central core (160 kDa) and to the cleaved-off tentacles (48 kDa). SAPSepharose specifically bound the 160-kDa fragment, suggesting that the central core of C4BP contains the binding site for SAP. In a quantitative affinity chromatography assay, the dissociation constants for binding of intact C4BP and of the 160-kDa central core fragment to SAP were found to be 30 and 70 nM, respectively. Recombinant C4BP composed of only ␣-chains bound SAP with similar affinity (K d ‫؍‬ 22 nM), whereas nonglycosylated recombinant ␣-chain C4BP (synthesized in the presence of tunicamycin) bound SAP with lower affinity (K d ‫؍‬ 126 nM). This suggests that the carbohydrate moiety of the central core of C4BP is important for binding of C4BP to SAP in contrast to the C4BP ␤-chain, which is not required. EDTA, heparin, and phosphorylethanolamine as well as a peptide comprising amino acids 27-39 of SAP were found to completely displace C4BP from the SAP matrix. Moreover, the immobilized SAP peptide bound C4BP in a reaction that, in contrast to the C4BP-SAP interaction, was not dependent on calcium.

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Section: Methodsmentioning

confidence: 99%

Section: C4b-binding Protein (C4bp)mentioning

confidence: 99%

Section: Sap-sepharose Affinity Chromatography Of C4bp and Itsmentioning

confidence: 99%

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Serum Amyloid P Component Binding to C4b-binding Protein

Frutos¹,

Härdig

Dahlbäck

1995

Journal of Biological Chemistry

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“…Three different batches of SAP were tested, and they gave similar results. The concentration of SAP was determined by absorbance at 280 nm using an extinction coefficient of 18.2 (27).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Alzheimer β-Peptide Fibril Formation by Serum Amyloid P Component

Janciauskiene

Frutos

Carlemalm

et al. 1995

Journal of Biological Chemistry

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A 39 -43-amino acid residue-long fragment (␤-peptide) from the amyloid precursor protein is the predominant component of amyloid deposits in the brain of individuals with Alzheimer's disease. Serum amyloid P component (SAP) is present in all types of amyloid, including that of Alzheimer's disease. We have used an in vitro model to study the effects of purified SAP on the fibril formation of synthetic Alzheimer ␤-peptide 1-42. SAP was found to inhibit fibril formation and to increase the solubility of the peptide in a dose-dependent manner. At a 5:1 molar ratio of A␤1-42 peptide to SAP, fibril formation was completely inhibited, and approximately 80% of the peptide remained in solution even after 4 days of incubation. At lower SAP concentrations, e.g. at peptide to SAP ratio of 1000:1, short fibrillar like structures, lacking amyloid characteristics, were formed. These structures frequently contained associated SAP molecules, suggesting that SAP binds to the polymerizing peptide in a reaction which prevented further fibril formation.

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“…To establish optimal calcium concentrations for binding of the protein to PMN cells, hSAP solution (200 pg/ ml) in NaCl/P, was titrated with Ca2' and the absorbance at 400nm was monitored [29]. Thus, fast aggregation was observed at an Cazc concentration of greater than 1.2 mM, whereas at levels less than 1.0 mM aggregation could not be detected even after 3 h at room temperature.…”

Section: Stability Of Hsap In Solutionmentioning

confidence: 99%

Binding of human serum amyloid P component (hSAP) to human neutrophils

Landsmann

Rosen

Pontet

et al. 1994

European Journal of Biochemistry

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Human serum amyloid P component (hSAP) and human C-reactive protein (hCRP) are normal serum constituents related to the pentraxin family of plasma proteins. hSAP has morphological and immunochemical identity and extensive sequence similarity to the amyloid P (AP) component found in normal tissues and particularly in amyloid deposits. hCRP and its proteolytic products have been previously shown to bind and to interact with various types of human leukocytes. Binding-displacement experiments with '251-labeled hSAP and hCRP show that both proteins have specific highaffinity binding sites on normal human polymorphonuclear leukocytes (PMN) and each can compete efficiently with the binding of the other. Scatchard analysis of hSAP-displacement curves reveals a heterogeneous population of hSAP-binding sites existing on the PMN cells, among them about 300000 low-affinity binding sites with K,% X M and about 30000 high-affinity binding sites with Kd 5 SXlO-*M. hAP was found to be degraded by enzymes from human neutrophils to yield a mixture of low-molecular-mass peptides, similarly to the case of CRP reported previously. The binding of hSAP can be efficiently inhibited by this peptide mixture. The results suggest that both hCRP and hSAP, together with related peptides, may participate in vivo in an unknown mechanism of regulation of human neutrophils.Serum amyloid P component (SAP) and C-reactive protein (CRP) belong to an evolutionary conserved family of human proteins, known as pentraxins [1-41. Human SAP (hSAP) is continuously present in human plasma in significant amounts (30-50 mg/l) and shows minor changes during the acute-phase response. In contrast, hCRP plasma levels in healthy individuals are less than 1 pg/ml and rise up to 1000-fold during inflammation [2-41. hSAP and hCRP share 60% sequence similarity [5]. Both proteins are arranged as planar pentamers, each consisting of five identical subunits. hCRP circulates in plasma as a single non-glycosylated pentamer (monomeric unit about 23 kDa) in coexistence with higher oligomers, whereas hSAP appears exclusively as a pair of glycosylated pentamers (monomeric unit about 25 kDa) oriented face-to-face as a decameric complex [2, 3, 6, 71. The aggregated tissue form of serum amyloid P, referred to as amyloid P (AP), is associated with nearly all types of amyloid fibrils (8-lo]. A number of features are shared by both hCRP and MAP, including, appearance in various sites of the body associated with tissue damage ; binding to nuclear constituents of disrupted cells and certain organic phos- -3, 8-15]. Extensive data have been accumulated concerning interactions of hCRP with human phagocytes, such as neutrophils [16-191, monocytes and macrophages [20-221. Initial receptor-mediated binding of hCRP to neutrophils is followed by its internalization and/or its proteolytic degradation by membrane and lysosomal proteases [23]. Proteolysis was found to yield a specific set of low-molecular-mass peptides (LMMP), some of which were shown to play a role in hCRPmediated modulation o...

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Calcium-dependent polymerization of human serum amyloid P component is inhibited by heparin and dextran sulfate

Cited by 25 publications

References 19 publications

Serum Amyloid P Component Binding to C4b-binding Protein

Serum Amyloid P Component Binding to C4b-binding Protein

Inhibition of Alzheimer β-Peptide Fibril Formation by Serum Amyloid P Component

Binding of human serum amyloid P component (hSAP) to human neutrophils

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