Native Human Serum Amyloid P Component is a Single Pentamer

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

doi:10.1111/j.1365-3083.1995.tb03562.x

Cited by 25 publications

(23 citation statements)

References 21 publications

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“…It has been proposed that SAP circulates as a decamer with two pentameric discs noncovalently bound face to face (Wood et al, 1988;Emsley et al, 1994). Other reports claim that SAP exists as a single pentamer in the body and that the decameric form is obtained only upon purification (Sorensen et al, 1995;Aquilina and Robinson 2003). SAP is synthesised and catabolized in the liver, and is present in human plasma and CSF at concentrations of ~ 40 µg/mL and 8.5 µg/ml , respectively.…”

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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“…Immobilization of either SAP [30,31] or Lselectin [32] may enhance their affinity for respective ligands. SAP has recently been described to be highly absorbed from plasma on biomedical materials such as polystyrene, promoting Ca 2+ -dependent leukocyte adhesion [31].…”

Section: Discussionmentioning

confidence: 99%

Binding of human serum amyloid P componentto L‐selectin

Stibenz

Gräfe²,

Debus³

et al. 2006

Eur J Immunol

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Serum concentrations of soluble L-selectin by far exceed those of other soluble adhesion molecules, and serum soluble L-selectin concentrations are remarkably stable upon prolonged storage. We present evidence for Ca 2+ -dependent binding interactions between human serum amyloid P (SAP), a proteolysis-resistant pentraxin glycoprotein, and L-selectin, as shown by surface plasmon resonance measurements, protein band shift assays in a native PAGE system, and after SDS-PAGE and membrane transfer. Monoclonal antibodies to L-selectin strongly reduced binding of biotinylated SAP to Lselectin-IgG chimeras immobilized on microtiter plates. As binding was reduced by prior glycopeptidase F treatment of L-selectin but not of SAP, it appears to be based on SAP lectin domain interactions with N-linked L-selectin carbohydrates. In freshly prepared human lymphocytes, SAP incubation induced expression of a b2 integrin neoepitope associated with high-affinity binding. This was partially blocked by preincubation with Fab fragments of two anti-L-selectin antibodies. In flow chamber experiments, SAP inhibited the adherence of human neutrophils to activated endothelium under shear stress. Thus, SAP binds to human L-selectin and affects Lselectin-dependent leukocyte-endothelial interactions.

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“…It has been proposed that SAP circulates as a decamer with two pentameric rings noncovalently bound [183,184]. However, other reports claim that SAP exists as a single pentamer in the body and that the decameric form is obtained only upon purification [185,186]. Human SAP shares approximately 51% amino acid homology with C-reactive protein, a classical human acute phase protein.…”

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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Native Human Serum Amyloid P Component is a Single Pentamer

Cited by 25 publications

References 21 publications

Extracellular Chaperones and Amyloids

Extracellular Chaperones and Amyloids

Binding of human serum amyloid P componentto L‐selectin

Extracellular Chaperones

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