scholarly journals Prediction from sequence comparisons of residues of factor H involved in the interaction with complement component C3b

1996 ◽  
Vol 315 (2) ◽  
pp. 523-531 ◽  
Author(s):  
Candida J. SOAMES ◽  
Antony J. DAY ◽  
Robert B. SIM
Keyword(s):  
Amino Acids ◽  
Human Factor ◽  
Factor H ◽  
Cdna Clones ◽  
Sequence Alignments ◽  
Sequence Comparisons ◽  
Factor I ◽  
Cofactor Activity ◽  
Human And Mouse ◽  
Bovine Factor

The amino acid sequence of the region of bovine factor H containing the C3b binding site has been derived from sequencing overlapping cDNA clones. A cDNA sequence encoding 669 amino acids was obtained. Like human and mouse factor H the sequence can be arranged into a number of internally homologous units (CPs), each of which is about 60 amino acids long and is based on a framework of four conserved cysteine residues. Bovine factor H is of the same molecular mass as human and mouse factor H, and is therefore likely to be composed of 20 contiguous CPs. Comparisons with human and mouse factor H indicate that the partial bovine sequence encodes CPs 2–12 inclusive of bovine factor H. Bovine factor H binds to human ammonia-treated C3 (causing thiolester cleavage) [C3(NH3)] and promotes the cleavage of human C3(NH3) in the presence of bovine factor I. Other studies indicate that CPs 2–5 of human factor H encompass the C3b binding and factor I cofactor activity site. Multiple sequence alignments of human factor H, mouse factor H (which also interacts with human C3b) and bovine factor H with CP modules whose structures have been determined experimentally, have been used to predict residues in the hypervariable loops of CPs 2–5 and to identify residues of potential importance in human C3 binding and factor I cofactor activity. Leu-17 and Gly-20 of CP 2, Ser-17, Ala-19, Glu-21, Asp-23 and Glu-25 of CP 3 and Lys-18 of CP 4 are all conserved between the three species. It may be that CPs 3 and 4 interact with C3(NH3) directly, whilst CPs 2 and 5 maintain the correct orientation for CPs 3 and 4 to interact.

Functional properties of the allotypes of mouse complement regulatory protein, factor H: Difference of compatibility of each allotype with human factor I

1993 ◽  
Vol 30 (9) ◽  
pp. 841-848 ◽  
Author(s):  
Okada Michiyo ◽  
Kojima Ayako ◽  
Takano Hiromi ◽  
Harada Yoshinobu ◽  
Nonaka Mayumi ◽  
...  
Keyword(s):  
Functional Properties ◽  
Human Factor ◽  
Regulatory Protein ◽  
Factor H ◽  
Complement Regulatory Protein ◽  
Factor I ◽  
Protein Factor

scholarly journals Human Factor H-Related Protein 5 Has Cofactor Activity, Inhibits C3 Convertase Activity, Binds Heparin and C-Reactive Protein, and Associates with Lipoprotein

2005 ◽  
Vol 174 (10) ◽  
pp. 6250-6256 ◽  
Author(s):  
Jennifer L. McRae ◽  
Thomas G. Duthy ◽  
Kim M. Griggs ◽  
Rebecca J. Ormsby ◽  
Peter J. Cowan ◽  
...  
Keyword(s):  
Human Factor ◽  
Factor H ◽  
Related Protein ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Cofactor Activity

Human factor H and C4b-binding protein serve as factor I-cofactors both encompassing inactivation of C3b and C4b

1995 ◽  
Vol 32 (5) ◽  
pp. 355-360 ◽  
Author(s):  
Tsukasa Seya ◽  
Kimiyo Nakamura ◽  
Takahisa Masaki ◽  
Chikako Ichihara-Itoh ◽  
Misako Matsumoto ◽  
...  
Keyword(s):  
Human Factor ◽  
Binding Protein ◽  
Factor H ◽  
Factor I

Monoclonal antibodies against the complement control protein Factor H (β1 H)

1983 ◽  
Vol 3 (12) ◽  
pp. 1119-1131 ◽  
Author(s):  
E. Sim ◽  
M. S. Palmer ◽  
M. Puklavec ◽  
R. B. Sim
Keyword(s):  
Monoclonal Antibodies ◽  
Human Factor ◽  
Factor H ◽  
Single Chain ◽  
Chain Molecules ◽  
Complement Control Protein ◽  
Protein Factor ◽  
Green Monkey ◽  
Cofactor Activity ◽  
Control Protein

Two mouse monoclonal antibodies against the human complement control protein, Factor H (β1H), are described. The antibodies are both IgG − γ1 - subclasses and are directed against different epitopes on the human Factor H molecule. One of the antibodies, MRC OX 24, increases the cofactor activity of Factor H in Factor I-mediated cleavage of soluble C3b. The second antibody, MRC OX 23, which has no effect alone, reduces the increase in cofactor activity observed in the presence of the first antibody. However, MRC OX 24 inhibits the binding of 125I-labelled Factor H to surface-bound C3b (EAC3b). Again MRC OX 23 alone does not have any effect but decreases the inhibition in 125I-Labelled Factor H binding to EAC3b observed with MRC OX 24. These studies show clearly that the interaction of Factor H with soluble C3b is different to its interaction with surface-bound C3b. In an indirect immunoprecipitation system using these monoclonal antibodies, single-chain molecules of 150 000 mol. wt. are specifically precipitated from human serum and also from the sera of other primates - rhesus monkey, cynomolgus monkey, and African green monkey. There was no precipitation from sera of cow, pig, sheep, chick, or rabbit. Using a radioimmunoassay with radiolabelled monoclonal MRC OX 23, the concentration of Factor H in human plasma was determined.

THE COMPLETE AMINO ACID SEQUENCE OF HUMAN FACTOR V

1987 ◽  
Author(s):  
Richard J Jenny ◽  
Debra D Pittman ◽  
John J Toole ◽  
Ronald W Kriz ◽  
Randal J Kaufman ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Factor Viii ◽  
Untranslated Region ◽  
Human Factor ◽  
Leader Peptide ◽  
Cdna Clones ◽  
Factor V ◽  
Human Factor Viii

cDNA clones encoding human factor V have been isolated and sequenced. The cDNA sequence of factor V obtained from overlapping clones includes a 6672 bp coding region, a 90 bp 5'-untranslated region and a 163 bp 3’-untranslated region including a poly-A tail. The deduced amino acid sequence consists of 2224 amino acids including a 28 amino acid leader peptide. A direct comparison to human factor VIII reveals considerable homology between both proteins with respect to amino acid sequence and domain structure. A triplicated "A" domain and duplicated "C" domain show an approximate 40% identity to the corresponding domains in factor VIII. Factor V and Factor VIII both possess a heavily glycosylated B domain that separates the heavy and light chains of the activated cofactors, although no significant homology is observed in this region. The B domain of factor V contains 35 tandem and approximately 9 additional semi - conserved repeats of nine amino acids of the form (D-L-S-Q-T-T-L-S-P) and 2 additional semi-conserved repeats of 17 amino acids. Factor V contains 37 potential N-linked glycosylation sites, 25 of which are in the B domain, and a total of 19 cysteine residues. By direct comparison to amino acid sequence obtained from both human and bovine factor V, the thrombin (IIa) cleavage sites have been assigned as Arg-709/Ser-710, Arg-1018/Thr-1019, and Are-1545/Ser-1546.(Supported by NIH Grant HL-34575)

scholarly journals Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins.

1988 ◽  
Vol 167 (3) ◽  
pp. 1047-1066 ◽  
Author(s):  
J J Weis ◽  
L E Toothaker ◽  
J A Smith ◽  
J H Weis ◽  
D T Fearon
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Epstein Barr Virus ◽  
Binding Proteins ◽  
Gene Sequence ◽  
B Lymphocyte ◽  
Factor H ◽  
Cdna Clones ◽  
Barr Virus ◽  
Epstein Barr

Human complement receptor type 2 (CR2) is the B lymphocyte receptor for C3d and the Epstein-Barr virus. This protein is also a member of a family of C3b/C4b binding proteins that regulate complement activation, comprise tandemly repeated 60-75 amino acid sequences, and whose genes map to band q32 on chromosome 1. Overlapping cDNA clones encoding the entire human CR2 protein have been isolated from a human tonsillar cDNA library. The derived amino acid sequence of 1,032 residues encodes a peptide of 112,716 mol wt. A signal peptide was identified, followed by 15 copies of the short consensus repeat (SCR) structure common to the C3/C4 binding protein family. The entire extracellular portion of the protein comprised SCRs, thus, the ligand binding sites both for C3d and the EBV protein gp350/220 are positioned within this structure. Immediately following the final SCR was a transmembrane sequence of 24 amino acids and a cytoplasmic region of 34 amino acids. One of five cDNA clones isolated contained an additional SCR, providing evidence for alternative mRNA splicing or gene products of different human alleles. The CR2 cDNAs were used to isolate CR2-specific genomic phage. The entire CR2 coding sequences were found within 20 kb of human DNA. Analysis of the CR2 cDNA sequence indicated that CR2 contained internally homologous regions and suggested that CR2 arose by duplication of a primordial gene sequence encoding four SCRs. Comparison of the CR2 peptide sequence with those of other members of the gene family has identified many regions highly homologous with human CR1, fewer with C4bp and decay accelerating factor, and very few with factor H, and suggested that CR2 and CR1 arose by duplication of the same ancestral gene sequence. The homology between CR2 and CR1 extended to the transmembrane and cytoplasmic regions, suggesting that these sequences were derived from a common membrane-bound precursor.

Effects of zinc on factor I cofactor activity of C4b-binding protein and factor H

2003 ◽  
Vol 418 (2) ◽  
pp. 108-118 ◽  
Author(s):  
Anna M Blom ◽  
Lena Kask ◽  
Bala Ramesh ◽  
Andreas Hillarp
Keyword(s):  
Binding Protein ◽  
Factor H ◽  
Factor I ◽  
Cofactor Activity

scholarly journals Functional and antigenic properties of complement receptor type 2, CR2.

1987 ◽  
Vol 165 (5) ◽  
pp. 1424-1429 ◽  
Author(s):  
K Mitomo ◽  
T Fujita ◽  
K Iida
Keyword(s):  
Factor H ◽  
Regulatory Proteins ◽  
Complement Receptor ◽  
Supporting Evidence ◽  
Complement Cascade ◽  
Factor I ◽  
Antigenic Properties ◽  
Membrane Bound ◽  
Cofactor Activity

This is the first report demonstrating that C3d receptor (CR2) has functional activity in regulating complement cascade. Purified CR2 was examined for its cofactor activity in factor I-mediated cleavage of membrane-bound iC3b. CR2 plus C3b inactivator (I) released C3c from EA 125I-iC3b, and the release was inhibited when CR2 was preincubated with OKB7 monoclonal anti-CR2. Furthermore, immunoelectroblotting analysis showed crossreactivity of CR2 with 57H anti-CR1. These results indicate that CR2 has functional and antigenic similarity to CR1, thus providing a supporting evidence for placement of CR2 as a member of the recently defined gene family of C3- and C4-regulatory proteins composed of CR1, C4-binding protein, and factor H.

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.

scholarly journals Localization of the complement-component-C3b-binding site and the cofactor activity for factor I in the 38kDa tryptic fragment of factor H

1984 ◽  
Vol 224 (2) ◽  
pp. 389-398 ◽  
Author(s):  
J Alsenz ◽  
J D Lambris ◽  
T F Schulz ◽  
M P Dierich
Keyword(s):  
Binding Site ◽  
Gel Filtration ◽  
Fluid Phase ◽  
Factor H ◽  
Tryptic Fragment ◽  
Factor I ◽  
Close Proximity ◽  
Cofactor Activity ◽  
A Site ◽  
Sepharose 4B

Trypsin treatment of human factor H (H160) [enzyme/substrate ratio 1:100 (w/w), 30 min, 37 degrees C] generated a 38 kDa (H38) and a 142 kDa (H142) fragment linked by disulphide bonds (H38/142). The fragments were purified by reduction with 2-mercapto-ethanol, gel filtration on a Sephadex G-200 column and affinity chromatography with monoclonal anti-(factor H) antibody coupled to Sepharose 4B. This monoclonal antibody bound to a site in the 38 kDa fragment. To localize the C3b binding site in factor H we used two enzyme-linked immunosorbent assays (e.l.i.s.a.). For the first test, e.l.i.s.a. plates were coated with C3b; H160, H38/142, H38 and H142 were added, and their binding was monitored by goat anti-(factor H) and peroxidase-labelled rabbit anti-goat antibodies. Only intact factor H bound to the C3b-coated plates. For the second test, e.l.i.s.a. plates were coated with comparable amounts of factor H or its fragments, and C3b was offered at several dilutions. In contrast with the results from the first assay, C3b bound to intact factor H, H38/142 and H38 but not to H142, thus characterizing H38 as the fragment carrying the C3b-binding site. To identify the fragment responsible for the cofactor activity of factor H (cleavage of fluid-phase C3b by factor I), 125I-C3b was incubated with either H38 or H142 and factor I. H142 had no cofactor activity, whereas H38 had the same cofactor function as intact H. To further investigate the relationship between the C3b-binding site and the site of factor H essential for its cofactor activity, we made use of monoclonal antibodies directed against the H38. Those antibodies inhibiting the binding of C3b to H160 also inhibited the cofactor function, whereas those without effect on the C3b binding also did not interfere with the cofactor activity. This suggests that the C3b-binding site and the site essential for the cofactor activity of factor H are both localized in the 38 kDa tryptic fragment of factor H in close proximity or are identical.

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