scholarly journals Structural gene for human membrane cofactor protein (MCP) of complement maps to within 100 kb of the 3' end of the C3b/C4b receptor gene.

1989 ◽  
Vol 169 (2) ◽  
pp. 597-602 ◽  
Author(s):  
N S Bora ◽  
D M Lublin ◽  
B V Kumar ◽  
R D Hockett ◽  
V M Holers ◽  
...  
Keyword(s):  
Structural Gene ◽  
Complement System ◽  
Receptor Gene ◽  
Chromosome 1 ◽  
Membrane Cofactor Protein ◽  
Structural Genes ◽  
Dna Fragment ◽  
Gene Maps ◽  
The Complement System

The structural gene for membrane cofactor protein (MCP), a widely distributed C3b/C4b binding regulatory glycoprotein of the complement system, has been mapped to the same locus as the structural genes for CR1, CR2, DAF, and C4bp. The order of the genes within an approximately 800-kb DNA fragment on the long arm of chromosome 1 is MCP-CR1-CR2-DAF-C4bp. Further, the MCP gene maps to within 100 kb of 3' end of the CR1 gene.

scholarly journals Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117840 ◽  
Author(s):  
A. Inkeri Lokki ◽  
Tia Aalto-Viljakainen ◽  
Seppo Meri ◽  
Hannele Laivuori
Keyword(s):  
Genetic Analysis ◽  
Complement System ◽  
Membrane Cofactor Protein ◽  
The Complement System

scholarly journals The Sea Star Igkappa Gene and The Ophuirid Igkappa Gene Vaccinations to HRP (Horse-radish Peroxydase)

2019 ◽  
Vol 4 (3) ◽  
Keyword(s):  
Complement System ◽  
Receptor Gene ◽  
Fc Receptor ◽  
Sea Star ◽  
Asterias Rubens ◽  
Genomic Studies ◽  
First Time ◽  
The Complement System

The main point of the sea star immunology, of the ophuirid immunology remain the discovery of the INVERTEBRATE PRIMITIVE ANTIBODY (IPA), the IGKAPPA GENES, with Ig sites which imply the COMPLEMENT SYSTEM, to be initiated: 9 component genes from C1 to C9 have been updated these last years, in sea star genome, in ophuirid one. These primitive antibodies were obtained after immunizations to the enzyme HRP (Horse-radish peroxydase). It is the first time we observe vaccinations in invertebrates. We have discovered, for the first time also, in these same Invertebrate a FC receptor gene, a Fab gene which corroborate the presence of IPA. The transcriptomes are given. It is the first time, we can speak of Adaptative Immunity, in Echinoderms, in Invertebrates Since many years, even since a century long, the notion of Antibody was out of the speech of immunologists. To speak of that made you as an outlaw. It is time to look with genomic studies which confirm which assert now evidence that 3 classes of Echinoderms out of 5 possess an Igkappa gene, a FC receptor gene. I recall these classent: the Asterids with Asterias rubens, the Ophuirids with Ophiocomina nigra and the Crinoïds.

scholarly journals Functional properties of membrane cofactor protein of complement

1989 ◽  
Vol 264 (2) ◽  
pp. 581-588 ◽  
Author(s):  
T Seya ◽  
J P Atkinson
Keyword(s):  
Complement System ◽  
Fluid Phase ◽  
Factor H ◽  
Classical Pathway ◽  
Membrane Cofactor Protein ◽  
Cleavage Reaction ◽  
Factor I ◽  
Thioester Bond ◽  
Cofactor Activity ◽  
The Complement System

Membrane cofactor protein (MCP or gp45-70) of the complement system is a cofactor for factor I-mediated cleavage of fluid-phase C3b and C3b-like C3, which opens the thioester bond. In the present study the activity of MCP was further characterized. Unexpectedly, in the absence of factor I, MCP stabilized the alternative- and, to a lesser extent, the classical-pathway cell-bound C3 convertases and thereby enhanced C3b deposition. Soluble MCP, if added exogenously, hardly functioned as cofactor for the cleavage of erythrocyte-bound C3b to iC3b; i.e. its activity, compared with the cofactor activity of factor H, was inefficient, since less than 10% of the bound C3b was MCP-sensitive. Further, exogenously added soluble MCP was also a weak cofactor for the cleavage of C3b bound to zymosan. Likewise, factor I, in the presence of cells bearing MCP, cleaved fluid-phase C3b inefficiently. These results imply that MCP has very little extrinsic cofactor activity for factor I. In contrast, exogenously added MCP and factor I mediated efficient cleavage of erythrocyte-bound C3b if the concentration of Nonidet P40 was sufficient to solubilize the cells. Interestingly, soluble MCP and factor I degraded C3b attached to certain solubilized acceptor membrane molecules more readily than others. The cleavage reaction of fluid-phase and cell-bound C3b by soluble MCP and factor I produced iC3b, but no C3c and C3dg. These and prior data indicate that soluble MCP has potent cofactor activity for fluid-phase C3b or C3b bound to solubilized molecules, but acts inefficiently towards C3b on other cells. This functional profile is unique for a C3b/C4b binding protein and, taken together with its wide tissue distribution, suggests an important role for MCP in the regulation of the complement system.

Protein S and C4b-Binding Protein: Components Involved in the Regulation of the Protein C Anticoagulant System

1991 ◽  
Vol 66 (01) ◽  
pp. 049-061 ◽  
Author(s):  
Björn Dahlbäck
Keyword(s):  
Vitamin K ◽  
Complement System ◽  
Protein C ◽  
Protein S ◽  
High Affinity ◽  
Anticoagulant System ◽  
Dependent Protein ◽  
The Complement System ◽  
Β Chain ◽  
Dependent Domain

SummaryThe protein C anticoagulant system provides important control of the blood coagulation cascade. The key protein is protein C, a vitamin K-dependent zymogen which is activated to a serine protease by the thrombin-thrombomodulin complex on endothelial cells. Activated protein C functions by degrading the phospholipid-bound coagulation factors Va and VIIIa. Protein S is a cofactor in these reactions. It is a vitamin K-dependent protein with multiple domains. From the N-terminal it contains a vitamin K-dependent domain, a thrombin-sensitive region, four EGF)epidermal growth factor (EGF)-like domains and a C-terminal region homologous to the androgen binding proteins. Three different types of post-translationally modified amino acid residues are found in protein S, 11 γ-carboxy glutamic acid residues in the vitamin K-dependent domain, a β-hydroxylated aspartic acid in the first EGF-like domain and a β-hydroxylated asparagine in each of the other three EGF-like domains. The EGF-like domains contain very high affinity calcium binding sites, and calcium plays a structural and stabilising role. The importance of the anticoagulant properties of protein S is illustrated by the high incidence of thrombo-embolic events in individuals with heterozygous deficiency. Anticoagulation may not be the sole function of protein S, since both in vivo and in vitro, it forms a high affinity non-covalent complex with one of the regulatory proteins in the complement system, the C4b-binding protein (C4BP). The complexed form of protein S has no APC cofactor function. C4BP is a high molecular weight multimeric protein with a unique octopus-like structure. It is composed of seven identical α-chains and one β-chain. The α-and β-chains are linked by disulphide bridges. The cDNA cloning of the β-chain showed the α- and β-chains to be homologous and of common evolutionary origin. Both subunits are composed of multiple 60 amino acid long repeats (short complement or consensus repeats, SCR) and their genes are located in close proximity on chromosome 1, band 1q32. Available experimental data suggest the β-chain to contain the single protein S binding site on C4BP, whereas each of the α-chains contains a binding site for the complement protein, C4b. As C4BP lacking the β-chain is unable to bind protein S, the β-chain is required for protein S binding, but not for the assembly of the α-chains during biosynthesis. Protein S has a high affinity for negatively charged phospholipid membranes, and is instrumental in binding C4BP to negatively charged phospholipid. This constitutes a novel mechanism for control of the complement system on phospholipid surfaces. Recent findings have shown circulating C4BP to be involved in yet another calcium-dependent protein-protein interaction with a protein known as the serum amyloid P-component (SAP). The binding sites on C4BP for protein S and SAP are independent. SAP, which is a normal constituent in plasma and in tissue, is a so-called pentraxin being composed of 5 non-covalently bound 25 kDa subunits. It is homologous to C reactive protein (CRP) but its function is not yet known. The specific high affinity interactions between protein S, C4BP and SAP suggest the regulation of blood coagulation and that of the complement system to be closely linked.

Stimulated Glanzmann’s Thrombasthenia Platelets Produce Microvesicles

1995 ◽  
Vol 74 (06) ◽  
pp. 1533-1540 ◽  
Author(s):  
Pål André Holme ◽  
Nils Olav Solum ◽  
Frank Brosstad ◽  
Nils Egberg ◽  
Tomas L Lindahl
Keyword(s):  
Complement System ◽  
Shape Change ◽  
Annexin V ◽  
Platelet Surface ◽  
Glanzmann’S Thrombasthenia ◽  
Large Numbers ◽  
Glanzmann's Thrombasthenia ◽  
Series Of Experiments ◽  
The Complement System ◽  
Number Of Particles

SummaryThe mechanism of formation of platelet-derived microvesicles remains controversial.The aim of the present work was to study the formation of microvesicles in view of a possible involvement of the GPIIb-IIIa complex, and of exposure of negatively charged phospholipids as procoagulant material on the platelet surface. This was studied in blood from three Glanzmann’s thrombasthenia patients lacking GPIIb-IIIa and healthy blood donors. MAb FN52 against CD9 which activates the complement system and produces microvesicles due to a membrane permeabilization, ADP (9.37 μM), and the thrombin receptor agonist peptide SFLLRN (100 μM) that activates platelets via G-proteins were used as inducers. In a series of experiments platelets were also preincubated with PGE1 (20 μM). The number of liberated microvesicles, as per cent of the total number of particles (including platelets), was measured using flow cytometry with FITC conjugated antibodies against GPIIIa or GPIb. Activation of GPIIb-IIIa was detected as binding of PAC-1, and exposure of aminophospholipids as binding of annexin V. With normal donors, activation of the complement system induced a reversible PAC-1 binding during shape change. A massive binding of annexin V was seen during shape change as an irreversible process, as well as formation of large numbers of microvesicles (60.6 ±2.7%) which continued after reversal of the PAC-1 binding. Preincubation with PGE1 did not prevent binding of annexin V, nor formation of microvesicles (49.5 ± 2.7%), but abolished shape change and PAC-1 binding after complement activation. Thrombasthenic platelets behaved like normal platelets after activation of complement except for lack of PAC-1 binding (also with regard to the effect of PGE1 and microvesicle formation). Stimulation of normal platelets with 100 μM SFLLRN gave 16.3 ± 1.2% microvesicles, and strong PAC-1 and annexin V binding. After preincubation with PGE1 neither PAC-1 nor annexin V binding, nor any significant amount of microvesicles could be detected. SFLLRN activation of the thrombasthenic platelets produced a small but significant number of microvesicles (6.4 ± 0.8%). Incubation of thrombasthenic platelets with SFLLRN after preincubation with PGE1, gave results identical to those of normal platelets. ADP activation of normal platelets gave PAC-1 binding, but no significant annexin V labelling, nor production of microvesicles. Thus, different inducers of the shedding of microvesicles seem to act by different mechanisms. For all inducers there was a strong correlation between the exposure of procoagulant surface and formation of microvesicles, suggesting that the mechanism of microvesicle formation is linked to the exposure of aminophospholipids. The results also show that the GPIIb-IIIa complex is not required for formation of microvesicles after activation of the complement system, but seems to be of importance, but not absolutely required, after stimulation with SFLLRN.

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