Pentraxins

Last updated
Pentaxin family
CRP pretty.png
CRP drawn from PDB: 1B09
Identifiers
SymbolPentaxin
Pfam PF00354
InterPro IPR001759
PROSITE PDOC00261
SCOP2 1sac / SCOPe / SUPFAM
CDD cd00152
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1lim D:32-237 2a3w F:26-219 2a3x H:26-219

1lgn C:26-219 2a3y D:26-219 1gyk A:26-219 1sac C:26-219 1has B:29-222 1crv E:25-220

Contents

1lj7 D:25-220 1b09 C:25-220 1gnh A:25-220

Pentraxins (PTX), also known as pentaxins, are an evolutionary conserved family of proteins characterised by containing a pentraxin protein domain. Proteins of the pentraxin family are involved in acute immunological responses. [1] They are a class of pattern recognition receptors (PRRs). They are a superfamily of multifunctional conserved proteins, some of which are components of the humoral arm of innate immunity and behave as functional ancestors of antibodies (Abs). They are known as classical acute phase proteins (APP), known for over a century. [2]

Structure

Pentraxins are characterised by calcium dependent ligand binding and a distinctive flattened β-jellyroll structure similar to that of the legume lectins. [3] The name "pentraxin" is derived from the Greek word for five ( πέντε , pente) and axle (axis) relating to the radial symmetry of five monomers forming a ring approximately 95Å across and 35Å deep observed in the first members of this family to be identified. The "short" pentraxins include Serum Amyloid P component (SAP) and C reactive protein (CRP). The "long" pentraxins include PTX3 (a cytokine modulated molecule) and several neuronal pentraxins.

Family members

Three of the principal members of the pentraxin family are serum proteins: namely, CRP, [4] SAP, [5] and hamster female protein (FP). [6] PTX3 (or TSG-14) protein is a cytokine-induced protein that is homologous to CRPs and SAPs.

C-reactive protein

C-reactive protein is expressed during the acute phase response to tissue injury or inflammation in mammals. The protein resembles antibody and performs several functions associated with host defence: it promotes agglutination, bacterial capsular swelling and phagocytosis, and activates the classical complement pathway through its calcium-dependent binding to phosphocholine. [4] CRPs have also been sequenced in an invertebrate, Limulus polyphemus (Atlantic horseshoe crab), where they are a normal constituent of the hemolymph.

Pentraxin 3

Pentraxin 3 (PTX3) is an acute phase protein whose levels rise during severe infections in humans. In case of central nervous system infections PTX3 helps distinguishes between bacterial and aseptic meningoencephalitis. It is significantly higher in bacterial meningoencephalitis. [7]

Serum amyloid P component

Serum amyloid P component is a vertebrate protein that is identical to tissue forms of amyloid P component. It is found in all types of amyloid deposits, in glomerular basement membrane and in elastic fibres in blood vessels. SAP binds to various lipoprotein ligands in a calcium-dependent manner, and it has been suggested that, in mammals, this may have important implications in atherosclerosis and amyloidosis. [5]

Hamster female protein

Hamster female protein is a SAP homologue found in Mesocricetus auratus (the Golden hamster). The concentration of this plasma protein is altered by sex steroids and stimuli that elicit an acute phase response. [6]

Nervous system

Pentraxin proteins expressed in the nervous system are neural pentraxin I (NPTXI) and II (NPTXII). [8] NPTXI and NPTXII are homologous and can exist within one species. It is suggested that both proteins mediate the uptake of synaptic macromolecules and play a role in synaptic plasticity. Apexin, a sperm acrosomal protein, is a homologue of NPTXII found in Cavia porcellus (Guinea pig). [9]

Human

Human genes encoding proteins that contain this domain include:

Related Research Articles

<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

<span class="mw-page-title-main">C-reactive protein</span> Mammalian protein found in humans

C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells in order to activate the complement system via C1q.

<span class="mw-page-title-main">Acute-phase protein</span> Class of proteins involved in inflammation

Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase or decrease in response to inflammation. This response is called the acute-phase reaction. The acute-phase reaction characteristically involves fever, acceleration of peripheral leukocytes, circulating neutrophils and their precursors. The terms acute-phase protein and acute-phase reactant (APR) are often used synonymously, although some APRs are polypeptides rather than proteins.

<span class="mw-page-title-main">Procalcitonin</span> Precursor of the peptide hormone calcitonin

Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It arises once preprocalcitonin is cleaved by endopeptidase. It was first identified by Leonard J. Deftos and Bernard A. Roos in the 1970s. It is composed of 116 amino acids and is produced by parafollicular cells of the thyroid and by the neuroendocrine cells of the lung and the intestine.

<span class="mw-page-title-main">Innate immune system</span> One of the two main immunity strategies

The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.

<span class="mw-page-title-main">Serum amyloid P component</span> Protein-coding gene in the species Homo sapiens

The serum amyloid P component (SAP) is the identical serum form of the amyloid P component (AP), a 25 kDa pentameric protein first identified as the pentagonal constituent of in vivo pathological deposits called "amyloid". APCS is its human gene.

C4b-binding protein (C4BP) is a protein complex involved in the complement system where it acts as inhibitor. C4BP has an octopus-like structure with a central stalk and seven branching alpha-chains. The main form of C4BP in human blood is composed of 7 identical alpha-chains and one unique beta-chain, which in turn binds anticoagulant, vitamin K-dependent protein S.

Sulfatide, also known as 3-O-sulfogalactosylceramide, SM4, or sulfated galactocerebroside, is a class of sulfolipids, specifically a class of sulfoglycolipids, which are glycolipids that contain a sulfate group. Sulfatide is synthesized primarily starting in the endoplasmic reticulum and ending in the Golgi apparatus where ceramide is converted to galactocerebroside and later sulfated to make sulfatide. Of all of the galactolipids that are found in the myelin sheath, one fifth of them are sulfatide. Sulfatide is primarily found on the extracellular leaflet of the myelin plasma membrane produced by the oligodendrocytes in the central nervous system and in the Schwann cells in the peripheral nervous system. However, sulfatide is also present on the extracellular leaflet of the plasma membrane of many cells in eukaryotic organisms.

Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively at different levels or in response to inflammatory stimuli. These proteins are produced predominantly by the liver.

<span class="mw-page-title-main">Lipopolysaccharide binding protein</span> Protein in humans

Lipopolysaccharide binding protein (LBP) is a protein that in humans is encoded by the LBP gene.

<span class="mw-page-title-main">CCR2</span> Mammalian protein found in Homo sapiens

C-C chemokine receptor type 2 (CCR2 or CD192 is a protein that in humans is encoded by the CCR2 gene. CCR2 is a CC chemokine receptor.

<span class="mw-page-title-main">Lipocalin-2</span> Protein-coding gene in the species Homo sapiens

Lipocalin-2 (LCN2), also known as oncogene 24p3 or neutrophil gelatinase-associated lipocalin (NGAL), is a protein that in humans is encoded by the LCN2 gene. NGAL is involved in innate immunity by sequestering iron and preventing its use by bacteria, thus limiting their growth. It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and alimentary tracts. NGAL is used as a biomarker of kidney injury.

<span class="mw-page-title-main">PTX3</span>

Pentraxin-related protein PTX3 also known as TNF-inducible gene 14 protein (TSG-14) is a protein that in humans is encoded by the PTX3 gene.

<span class="mw-page-title-main">Formyl peptide receptor 2</span> Protein-coding gene in the species Homo sapiens

N-formyl peptide receptor 2 (FPR2) is a G-protein coupled receptor (GPCR) located on the surface of many cell types of various animal species. The human receptor protein is encoded by the FPR2 gene and is activated to regulate cell function by binding any one of a wide variety of ligands including not only certain N-Formylmethionine-containing oligopeptides such as N-Formylmethionine-leucyl-phenylalanine (FMLP) but also the polyunsaturated fatty acid metabolite of arachidonic acid, lipoxin A4 (LXA4). Because of its interaction with lipoxin A4, FPR2 is also commonly named the ALX/FPR2 or just ALX receptor.

<span class="mw-page-title-main">SAA2</span> Protein-coding gene in the species Homo sapiens

Serum amyloid A protein is a protein that in humans is encoded by the SAA2 gene.

<span class="mw-page-title-main">Serum amyloid A1</span> Protein-coding gene in the species Homo sapiens

Serum amyloid A1 (SAA1) is a protein that in humans is encoded by the SAA1 gene. SAA1 is a major acute-phase protein mainly produced by hepatocytes in response to infection, tissue injury and malignancy. When released into blood circulation, SAA1 is present as an apolipoprotein associated with high-density lipoprotein (HDL). SAA1 is a major precursor of amyloid A (AA), the deposit of which leads to inflammatory amyloidosis.

<span class="mw-page-title-main">NPTX2</span> Protein-coding gene in the species Homo sapiens

Neuronal pentraxin-2 is a protein that in humans is encoded by the NPTX2 gene.

Sir Mark Brian Pepys is a South African-born British academic of medicine. He was until 2011 Professor of Medicine at University College London and Head of Medicine at the Hampstead Campus and the Royal Free Hospital.

Ficolins are pattern recognition receptors that bind to acetyl groups present in the carbohydrates of bacterial surfaces and mediate activation of the lectin pathway of the complement cascade.

Microglia are the primary immune cells of the central nervous system, similar to peripheral macrophages. They respond to pathogens and injury by changing morphology and migrating to the site of infection/injury, where they destroy pathogens and remove damaged cells.

References

  1. Gewurz H, Zhang XH, Lint TF (February 1995). "Structure and function of the pentraxins". Current Opinion in Immunology. 7 (1): 54–64. doi:10.1016/0952-7915(95)80029-8. PMID   7772283.
  2. Martinez de la Torre Y, Fabbri M, Jaillon S, Bastone A, Nebuloni M, Vecchi A, et al. (May 2010). "Evolution of the pentraxin family: the new entry PTX4". Journal of Immunology. 184 (9): 5055–64. doi: 10.4049/jimmunol.0901672 . PMID   20357257.
  3. Emsley J, White HE, O'Hara BP, Oliva G, Srinivasan N, Tickle IJ, et al. (January 1994). "Structure of pentameric human serum amyloid P component". Nature. 367 (6461): 338–45. Bibcode:1994Natur.367..338E. doi:10.1038/367338a0. PMID   8114934. S2CID   4284282.
  4. 1 2 Romero IR, Morris C, Rodriguez M, Du Clos TW, Mold C (May 1998). "Inflammatory potential of C-reactive protein complexes compared to immune complexes". Clinical Immunology and Immunopathology. 87 (2): 155–62. doi:10.1006/clin.1997.4516. PMID   9614930.
  5. 1 2 Li XA, Yutani C, Shimokado K (March 1998). "Serum amyloid P component associates with high density lipoprotein as well as very low density lipoprotein but not with low density lipoprotein". Biochemical and Biophysical Research Communications. 244 (1): 249–52. doi:10.1006/bbrc.1998.8248. PMID   9514915.
  6. 1 2 Coe JE, Ross MJ (August 1997). "Electrophoretic polymorphism of a hamster pentraxin, female protein (amyloid P component)". Scandinavian Journal of Immunology. 46 (2): 180–6. doi: 10.1046/j.1365-3083.1997.d01-109.x . PMID   9583999. S2CID   6361670.
  7. Zatta M, Di Bella S, Bottazzi B, Rossi F, D'Agaro P, Segat L, et al. (December 2019). "Determination of pentraxin 3 levels in cerebrospinal fluid during central nervous system infections". European Journal of Clinical Microbiology & Infectious Diseases. 39 (4): 665–670. doi:10.1007/s10096-019-03767-w. hdl: 11368/2972747 . PMID   31813079. S2CID   208812200.
  8. Omeis IA, Hsu YC, Perin MS (September 1996). "Mouse and human neuronal pentraxin 1 (NPTX1): conservation, genomic structure, and chromosomal localization". Genomics. 36 (3): 543–5. doi:10.1006/geno.1996.0503. PMID   8884281.
  9. Reid MS, Blobel CP (December 1994). "Apexin, an acrosomal pentaxin". The Journal of Biological Chemistry. 269 (51): 32615–20. PMID   7798266.
This article incorporates text from the public domain Pfam and InterPro: IPR001759