Binding of Complement Proteins C1q and C4bp to Serum Amyloid P Component (SAP) in Solid Contra Liquid Phase

Sørensen, Inge Juul; Andersen, Ove; Danielsen, Bente; Svehag, Sven‐Erik

doi:10.1046/j.1365-3083.1996.d01-326.x

Cited by 34 publications

(30 citation statements)

References 17 publications

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“…Each subunit monomer has two Ca 2+ -binding sites and shows Ca 2+ -dependent binding to many different ligands, including certain oligosaccharides, glycosaminoglycans (Hamazaki 1987), fibronectin , C-reactive protein (Swanson et al, 1992), aggregated IgG (Brown and Anderson 1993), C1q (Sorensen et al, 1996), complement C4-binding protein (Sorensen et al, 1996), DNA (Pepys and Butler 1987), chromatin (Breathnach et al, 1989), histones (Hicks et al, 1992), and phosphoethanolamine-containing compounds such as phosphatidylethanolamine (Emsley et al, 1994). Interaction with these ligands localises SAP to elastic microfibrils , glomerular and alveolar basement membrane, arterioles, bronchioles, sarcolemma of cardiac and smooth muscle (Dyck et al, 1980), and all forms of amyloid .…”

Section: Serum Amyloid P Componentmentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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The pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacerabate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ABSTRACTThe pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

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Section: Serum Amyloid P Componentmentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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“…In the presence of calcium ions, SAP can bind to several ligands such as amyloid fibrils of any type (4), agarose (8), heparin and dermatan sulfate (9), C1q (10,11), C4 binding protein (12,13), laminin (14), type V collagen (15), and phosphoethanolaminecontaining compounds such as phosphatidylethanolamine (16,17), DNA (18), chromatin (19,20), and histones (21,22).…”

Section: H Uman Serum Amyloid P Component (Sap)mentioning

confidence: 99%

Chromatin-Independent Binding of Serum Amyloid P Component to Apoptotic Cells

Familian

Zwart

et al. 2001

The Journal of Immunology

111

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Human serum amyloid P component (SAP) is a glycoprotein structurally belonging to the pentraxin family of proteins, which has a characteristic pentameric organization. Mice with a targeted deletion of the SAP gene develop antinuclear Abs, which was interpreted as evidence for a role of SAP in controlling the degradation of chromatin. However, in vitro SAP also can bind to phosphatidylethanolamine, a phospholipid which in normal cells is located mainly in the inner leaflet of the cell membrane, to be translocated to the outer leaflet of the cell membrane during a membrane flip-flop. We hypothesized that SAP, because of its specificity for phosphatidylethanolamine, may bind to apoptotic cells independent of its nuclear binding. Calcium-dependent binding of SAP to early, nonpermeable apoptotic Jurkat, SKW, and Raji cells was indeed observed. Experiments with flip-flopped erythrocytes confirmed that SAP bound to early apoptotic cells via exposed phosphatidylethanolamine. Binding of SAP was stronger to late, permeable apoptotic cells. Experiments with enucleated neutrophils, with DNase/RNase treatment of late apoptotic Jurkat cells, and competition experiments with histones suggested that binding of SAP to late apoptotic cells was largely independent of chromatin. Confocal laser microscopic studies indeed suggested that SAP bound to these apoptotic cells mainly via the blebs. Thus, this study shows that SAP binds to apoptotic cells already at an early stage, which raises the possibility that SAP is involved in dealing with apoptotic cells in vivo.

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“…Although to date no clear biological function has been ascribed to SAP, it is known to interact with a diverse range of molecules in vitro. For example, SAP binds to glycosaminoglycans [187], DNA and chromatin [188][189][190], complement components [191,192], fibronectin [193], C-reactive protein [194], aggregated IgG [195], phosphatidylethanolamine [196] and endotoxin [183,197]. Of particular interest in the current context, SAP binds highly specifically to amyloid and is universally found in amyloid deposits [85][86][87][88]191].…”

Section: Serum Amyloid P Componentmentioning

confidence: 99%

Extracellular Chaperones

Dabbs

Wyatt

Yerbury

et al. 2010

Topics in Current Chemistry

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The maintenance of the levels and correct folding state of proteins (proteostasis) is a fundamental prerequisite for life. Life has evolved complex mechanisms to maintain proteostasis and many of these that operate inside cells are now well understood. The same cannot yet be said of corresponding processes in extracellular fluids of the human body, where inappropriate protein aggregation is known to underpin many serious diseases such as Alzheimer's disease, type II diabetes and prion diseases. Recent research has uncovered a growing family of abundant extracellular chaperones in body fluids which appear to selectively bind to exposed regions of hydrophobicity on misfolded proteins to inhibit their toxicity and prevent them from aggregating to form insoluble deposits. These extracellular chaperones are also implicated in clearing the soluble, stabilized misfolded proteins from body fluids via receptor-mediated endocytosis for subsequent lysosomal degradation. Recent work also raises the possibility that extracellular chaperones may play roles in modulating the immune response. Future work will better define the in vivo functions of extracellular chaperones in proteostasis and immunology and pave the way for the development of new treatments for serious diseases.

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Binding of Complement Proteins C1q and C4bp to Serum Amyloid P Component (SAP) in Solid Contra Liquid Phase

Cited by 34 publications

References 17 publications

Extracellular Chaperones and Amyloids

Extracellular Chaperones and Amyloids

Chromatin-Independent Binding of Serum Amyloid P Component to Apoptotic Cells

Extracellular Chaperones

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