Sequence analysis of a cDNA clone encoding the C-terminal end of human complement factor H

1987 ◽  
Vol 7 (3) ◽  
pp. 201-207 ◽  
Author(s):  
A. J. Day ◽  
J. Ripoche ◽  
A. Lyons ◽  
B. McIntosh ◽  
T. J. R. Harris ◽  
...  
Keyword(s):  
Amino Acids ◽  
Tertiary Structure ◽  
Regulatory Protein ◽  
Peptide Sequencing ◽  
Factor H ◽  
Cdna Libraries ◽  
Complement Factor ◽  
Protein Factor ◽  
The Complement System ◽  
Full Length Clone

Peptide sequencing of the complement system regulatory protein, factor H, permitted the synthesis of a mixed sequence oligonucleotide probe. Human liver cDNA libraries were screened and factor H-specific clones selected. No full-length clone was obtained, but the largest available clone, R2a, was found to encode the C-terminal 657 amino acids of factor H. The derived amino acid sequence consists of 10 contiguous internally homologous segments, each about 60 amino acids long. Sequences homologous to these are found in several other complement and non-complement proteins. Such sequences are likely to represent a particular type of tertiary structure subunit.

scholarly journals M Protein of the Group A StreptococcusBinds to the Seventh Short Consensus Repeat of Human Complement Factor H

1998 ◽  
Vol 66 (4) ◽  
pp. 1427-1431 ◽  
Author(s):  
Timothy K. Blackmore ◽  
Vincent A. Fischetti ◽  
Tania A. Sadlon ◽  
Helena M. Ward ◽  
David L. Gordon
Keyword(s):  
Protein Binding ◽  
Binding Site ◽  
Regulatory Protein ◽  
Factor H ◽  
M Protein ◽  
Protein Binding Site ◽  
Enzyme Linked Immunosorbent Assay ◽  
Complement Factor ◽  
Heparin Binding ◽  
Protein Factor

ABSTRACT Streptococcus pyogenes evades complement by binding the complement-regulatory protein factor H (fH) via the central conserved C-repeat region of M protein. However, the corresponding binding region within fH has not previously been precisely localized. fH is composed of 20 conserved modules called short consensus repeats (SCRs), each of which contains approximately 60 amino acids. A series of fH truncated and deletion mutants were prepared, and their interaction with M6 protein was examined. The M protein binding site was initially localized to SCRs 6 to 15 as demonstrated by ligand dot blotting, chemical cross-linking, and enzyme-linked immunosorbent assay. SCR 7 was then shown to contain the M protein binding site, as a construct consisting of the first seven SCRs bound M protein but a construct containing the first six SCRs did not bind. In addition, deletion of SCR 7 from full-length fH abolished binding to M protein. SCR 7 is known to contain a heparin binding domain, and binding of fH to M6 protein was almost totally inhibited in the presence of 400 U of heparin per ml. These results localize the M6 protein binding site of fH to SCR 7 and indicate that it is in close proximity to the heparin binding site.

scholarly journals Low levels of serum complement factor H is associated with increasing progression of bronchiectasis

2019 ◽  
Vol 6 (7) ◽  
pp. 3286-3292 ◽  
Author(s):  
Abubakar Shettima ◽  
Muhammad M. Ibrahim
Keyword(s):  
Healthy Volunteers ◽  
Sandwich Elisa ◽  
Regulatory Protein ◽  
Serum Levels ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Elisa Technique ◽  
Low Levels ◽  
The Complement System

Introduction: Complement Factor H (CFH) is the major soluble regulatory protein that monitors activation and/or amplification of the complement system. Here, we assess serum levels of complement factor H (CFH) among patients, who were diagnosed with bronchiectasis. Methods: 115 subjects of 80 patients and 35 healthy volunteers were recruited for the study. Blood samples were collected and subjected to centrifugation in order to obtain the serum. The sensitive sandwich ELISA technique, specific for CFH was used for evaluation of CFH in the serum. Results: The age and Body Mass Index (BMI) (expressed as Mean+/-SEM (range)) of the observed bronchiectasis patients and healthy volunteers were 66+/-1.13, (30-86) years, 54+/-2.37 (27-84) years and 26.14 kg/m2, 27.4 kg/m2 respectively. CFH was detected in 27.0% of all subjects examined. It was found to be more common among bronchiectasis patients (18.26%) compared to healthy volunteers (8.70%) (F=0.9362; df=1; p<0.05). Mean CFH concentration was 17.0pg/ml and 9.0pg/ml in bronchiectasis patients and healthy volunteers respectively. FEV1% Pre. FEV1/VC% and CFH levels were found to decrease with increasing severity of bronchiectasis. The association between lung function, CFH levels and severity of disease among bronchiectasis patients was negative, strongly linear (r= -0.9316, r2 =0.8678) and statistically significant (p<0.0001). Conclusion: As such, it can be inferred that low level of compliment factor H is related to the progression of bronchiectasis.  

scholarly journals Human complement factor H deficiency associated with hemolytic uremic syndrome.

1998 ◽  
Vol 9 (12) ◽  
pp. 2318-2326
Author(s):  
N Rougier ◽  
M D Kazatchkine ◽  
J P Rougier ◽  
V Fremeaux-Bacchi ◽  
J Blouin ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Regulatory Protein ◽  
Large Deletion ◽  
Factor H ◽  
Pcr Analysis ◽  
Complement Factor ◽  
Human Complement ◽  
Protein Factor ◽  
Factor H Deficiency ◽  
Uremic Syndrome

This study reports on six cases of deficiency in the human complement regulatory protein Factor H (FH) in the context of an acute renal disease. Five of the cases were observed in children presenting with idiopathic hemolytic uremic syndrome (HUS). Two of the children exhibited a homozygous deficiency characterized by the absence of the 150-kD form of Factor H and the presence, upon immunoblotting, of the 42-kD Factor H-like protein 1 (FHL-1) and other FH-related protein (FHR) bands. Southern blot and PCR analysis of DNA of one patient with homozygous deficiency ruled out the presence of a large deletion of the FH gene as the underlying defect for the deficiency. The other four children presented with heterozygous deficiency and exhibited a normal immunoblotting pattern of proteins of the FH family. Factor H deficiency is the only complement deficiency associated with HUS. These observations suggest a role for FH and/or FH receptors in the pathogenesis of idiopathic HUS.

scholarly journals The N2N3 domains of ClfA, FnbpA, and FnbpB in Staphylococcus aureus bind to human complement factor H, and their antibodies enhance the bactericidal capability of human blood

2020 ◽  
Author(s):  
Xinrui Mao ◽  
Junghyun Kim ◽  
QingFeng Zhang ◽  
TingTing Jiang ◽  
Dong Ho Ahn ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Surface ◽  
Human Blood ◽  
Bacterial Cell ◽  
Regulatory Protein ◽  
Factor H ◽  
Complement Factor ◽  
Bacterial Cell Surface ◽  
Protein Factor

Abstract In the complement system, the opsonin C3b binds to the bacterial cell surface and mediates the opsonophagocytosis. However, the cell wall protein SdrE of Staphylococcus aureus inhibits the C3b activity by recruiting the complement regulatory protein factor H (fH). SdrE binds to fH via its N-terminal N2N3 domain, which are also found in six other staphylococcal cell wall proteins. In this study, we report that not only the N2N3 domain of SdrE but also those of ClfA, FnbpA, and FnbpB can bind to fH. When immobilized on a microplate, the N2N3 domains recruited fH and enhanced the factor I (fI)-mediated cleavage of C3b. When mixed with fH and S. aureus cells, the N2N3 domains inhibited the fH binding to S. aureus cells and reduced the fI-mediated C3b cleavage on the bacterial cell surface. The F(ab)′2 fragments of the rabbit N2N3 antibodies also inhibited the fH-binding to the S. aureus cell surface. When added to human blood, the N2N3 antibodies or the N2N3 domain proteins significantly increased the bactericidal activity. Based on these results, we conclude that, in S. aureus, not only SdrE but also ClfA, FnbpA, and FnbpB can contribute to the inhibition of C3b-mediated opsonophagocytosis.

scholarly journals The complete amino acid sequence of human complement factor H

1988 ◽  
Vol 249 (2) ◽  
pp. 593-602 ◽  
Author(s):  
J Ripoche ◽  
A J Day ◽  
T J R Harris ◽  
R B Sim
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Repeat Unit ◽  
Regulatory Protein ◽  
Factor H ◽  
Cdna Clones ◽  
Complement Factor ◽  
Human Complement ◽  
Complete Amino Acid Sequence

The complete amino acid sequence of the human complement system regulatory protein, factor H, has been derived from sequencing three overlapping cDNA clones. The sequence consists of 1213 amino acids arranged in 20 homologous units, each about 60 amino acids long, and an 18-residue leader sequence. The 60-amino-acid-long repetitive units are homologous with those found in a large number of other complement and non-complement proteins. Two basic C-terminal residues, deduced from the cDNA sequence, are absent from factor H isolated from outdated plasma. A tyrosine/histidine polymorphism was observed within the seventh homologous repeat unit of factor H. This is likely to represent a difference between the two major allelic variants of factor H. The nature of the cDNA clones indicates that there is likely to be an alternative splicing mechanism, resulting in the formation of at least two species of factor H mRNA.

scholarly journals Complement Regulatory Protein Factor H Is a Soluble Prion Receptor That Potentiates Peripheral Prion Pathogenesis

2017 ◽  
Vol 199 (11) ◽  
pp. 3821-3827 ◽  
Author(s):  
Sarah J. Kane ◽  
Taylor K. Farley ◽  
Elizabeth O. Gordon ◽  
Joshua Estep ◽  
Heather R. Bender ◽  
...  
Keyword(s):  
Regulatory Protein ◽  
Factor H ◽  
Complement Regulatory Protein ◽  
Protein Factor

scholarly journals Case Report: Lipoprotein Glomerulopathy Complicated by Atypical Hemolytic Uremic Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Lara Kollbrunner ◽  
Patricia Hirt-Minkowski ◽  
Javier Sanz ◽  
Elena Bresin ◽  
Thomas J. Neuhaus ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor ◽  
Inherited Disease ◽  
Lipoprotein Glomerulopathy ◽  
Gene Encoding ◽  
Alternative Complement ◽  
Uremic Syndrome ◽  
The Complement System

Lipoprotein glomerulopathy (LPG) is a rare inherited disease caused by mutations in the APOE gene, encoding apolipoprotein E (apoE). Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by overactivation of the alternative complement pathway. Here we report the case of a 21-year-old man with LPG who developed aHUS. A functional complement assay demonstrated an overactivation of the complement system. Complementary genetic analysis revealed a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. To the best of our knowledge, this is the first report of an aHUS in a patient with LPG.

Arg127 of complement regulatory protein Factor H is important for its secretion from human fibroblasts

2009 ◽  
Vol 46 (14) ◽  
pp. 2869
Author(s):  
José Antonio Tavares Albuquerque ◽  
Dayseanne Araújo Falcão ◽  
Lourdes Isaac
Keyword(s):  
Human Fibroblasts ◽  
Regulatory Protein ◽  
Factor H ◽  
Complement Regulatory Protein ◽  
Protein Factor

scholarly journals Identification of Potential Novel Interacting Partners for Coagulation Factor XIII B (FXIII-B) Subunit, a Protein Associated with a Rare Bleeding Disorder

2019 ◽  
Vol 20 (11) ◽  
pp. 2682 ◽  
Author(s):  
Sneha Singh ◽  
Mohammad Suhail Akhter ◽  
Johannes Dodt ◽  
Peter Volkers ◽  
Andreas Reuter ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Regulatory Protein ◽  
Coagulation Factor ◽  
Factor H ◽  
Complement C3 ◽  
Complement Factor ◽  
B Subunit ◽  
Coagulation Factor Xiii ◽  
A Subunit ◽  
Complement C1q

Coagulation factor XIII (FXIII) is a plasma-circulating heterotetrameric pro-transglutaminase complex that is composed of two catalytic FXIII-A and two protective/regulatory FXIII-B subunits. FXIII acts by forming covalent cross-links within a preformed fibrin clots to prevent its premature fibrinolysis. The FXIII-A subunit is known to have pleiotropic roles outside coagulation, but the FXIII-B subunit is a relatively unexplored entity, both structurally as well as functionally. Its discovered roles so far are limited to that of the carrier/regulatory protein of its partner FXIII-A subunit. In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification. Complement factor H was one of the co-excipients observed in this analysis. This was followed by performing pull down assays from plasma in order to detect the putative novel interacting partners for the FXIII-B subunit. Complement system proteins, like complement C3 and complement C1q, were amongst the proteins that were pulled down. The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association.

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