503 A GENETIC CODING VARIANT IN COMPLEMENT FACTOR B IS ASSOCIATED WITH INCREASED RISK FOR PERIANAL CROHN'S DISEASE AND LEADS TO AN AMINO ACID CHANGE IN THE LINKER REGION THAT IMPAIRS CLEAVAGE OF CFB, AND COMPLEMENT-DRIVEN PHAGOCYTOSIS

2021 ◽  
Vol 160 (6) ◽  
pp. S-100
Author(s):  
Marcy Akhlaghpour ◽  
Lisa S. Thomas ◽  
Talin Haritunians ◽  
Carol Landers ◽  
Stephan R. Targan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Change ◽  
Complement Factor ◽  
Factor B ◽  
Linker Region ◽  
Perianal Crohn’S Disease ◽  
Complement Factor B ◽  
Genetic Coding ◽  
Increased Risk ◽  
Perianal Crohn's Disease

scholarly journals The principal site of glycation of human complement factor B

1991 ◽  
Vol 274 (2) ◽  
pp. 473-480 ◽  
Author(s):  
M A Niemann ◽  
A S Bhown ◽  
E J Miller
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Sequence Data ◽  
Complement Factor ◽  
Human Complement ◽  
Factor B ◽  
Complement Factor B ◽  
Functional Regions ◽  
High Concentrations

Accumulating amino acid sequence data have made it increasingly evident that many essential complement proteins have potentially modifiable lysine residues in putative critical functional regions. Evidence is now presented that glucose is covalently attached to lysine-266 of purified human complement Factor B as a result of glycation. Purified B was treated with NaB3H4, which reduces such bound glucose to a mixture of radiolabelled hexitols. Amino acid analysis revealed the expected radiolabelled hexitol-lysine epimers. In addition, fluorography of dried gels resolving the major high-molecular-mass h.p.l.c.-fractionated CNBr-cleavage peptides of NaB3H4-reduced B indicated that this radioactivity was specifically associated with the 15 kDa fragment derived from the N-terminal region of fragment Bb. Amino acid sequence analysis suggested that the C-terminal lysine (residue 266 of B) of the N-terminal Lys-Lys doublet of this peptide is preferentially modified. If such glycation can subsequently be shown to occur in vivo, then perhaps this modification might also be found to affect the functional activity of B and offer a potential explanation for some of the immunopathological complications of diseases exposing key plasma proteins, such as this active-site-containing proteinase of the multimeric alternative-complement-pathway C3/C5 convertases, to long-term high concentrations of glucose, such as the decreased resistance to infection and impaired chemotaxis and phagocytosis characteristic of diabetes.

scholarly journals Amino acid sequence of the Bb fragment from complement Factor B. Sequence of the major cyanogen bromide-cleavage peptide (CB-II) and completion of the sequence of the Bb fragment

1983 ◽  
Vol 209 (1) ◽  
pp. 61-70 ◽  
Author(s):  
D L Christie ◽  
J Gagnon
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Serine Proteinase ◽  
Preceding Paper ◽  
Complete Sequence ◽  
Major Product ◽  
Activation Mechanism ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

The amino acid sequence of peptide CB-II, the major product (mol.wt. 30 000) of CNBr cleavage of fragment Bb from human complement Factor B, is given. The sequence was obtained from peptides derived by trypsin cleavage of peptide CB-II and clostripain digestion of fragment Bb. Cleavage of two Asn-Gly bonds in peptide CB-II was also found useful. These results, along with those presented in the preceding paper [Gagnon & Christie (1983) Biochem. J. 209, 51-60], yield the complete sequence of the 505 amino acid residues of fragment Bb. The C-terminal half of the molecule shows strong homology of sequence with serine proteinases. Factor B has a catalytic chain (fragment Bb) with a molecular weight twice that of proteinases previously described, suggesting that it is a novel type of serine proteinase, probably with a different activation mechanism.

Abstract 13047: Plasma Protein Expression and Incident Cvd, and the Role of Resilience: Results From the Mediators of Atherosclerosis in South Asians Living in America (masala) Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Long Ngo ◽  
Austin Argentieri ◽  
Simon Dillon ◽  
Alka M Kanaya ◽  
Alexandra Shields ◽  
...  
Keyword(s):  
Religious Coping ◽  
Immune Cell ◽  
South Asians ◽  
Information Criteria ◽  
Complement Factor ◽  
Plasma Samples ◽  
Factor B ◽  
Complement Factor B ◽  
Increased Risk ◽  
Negative Religious Coping

Introduction: Few proteomics studies have included non-white individuals, and none have explored the influence of resiliency resources on the association between proteins and cardiovascular disease (CVD). Religious and spiritual beliefs and practices are understudied resiliency resources that may attenuate the influence of proteins associated with increased risk of CVD. Methods: We conducted a nested case-control study using data from the MASALA Study. We used baseline plasma samples from 50 South Asian participants with incident CVD and 50 sex- and age-matched controls. We analyzed plasma samples by SOMAscan, an aptamer-based proteomics platform, for 1305 unique proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates. We assessed the influence of measures of spiritual practices on the association between proteins and incident CVD events. Results: We identified 36 proteins that were significantly dysregulated among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5, Low affinity immunoglobulin gamma Fc region receptor II-a, Complement factor B) associated with CVD after adjustment for diabetes (c-statistic=0.82). Negative religious coping significantly modified the effect of Contactin-5 and Complement factor B for risk of CVD. ( Table ) Conclusions: Three novel plasma proteins were associated with incident CVD, and negative religious coping significantly modified the effect, in this pilot study of South Asians. Further investigation is needed to understand proteomic profiles across diverse communities, and the role that resiliency resources in modifying the putative effect of proteomic signatures.

scholarly journals Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long H. Ngo ◽  
M. Austin Argentieri ◽  
Simon T. Dillon ◽  
Blake Victor Kent ◽  
Alka M. Kanaya ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Plasma Protein ◽  
Expression Profiles ◽  
South Asians ◽  
Predictive Biomarkers ◽  
Information Criteria ◽  
Blood Protein ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

AbstractBlood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.

scholarly journals The effects of metal ions and temperature on the interaction of cobra venom factor and human complement factor B.

1986 ◽  
Vol 261 (24) ◽  
pp. 11038-11044 ◽  
Author(s):  
P Hensley ◽  
M C O'Keefe ◽  
C J Spangler ◽  
J C Osborne ◽  
C W Vogel
Keyword(s):  
Metal Ions ◽  
Cobra Venom ◽  
Complement Factor ◽  
Human Complement ◽  
Cobra Venom Factor ◽  
Factor B ◽  
Complement Factor B

C3 Glomerulonephritis Associated With Complement Factor B Mutation

2015 ◽  
Vol 65 (3) ◽  
pp. 520-521 ◽  
Author(s):  
Sanjeev Sethi ◽  
Richard J.H. Smith ◽  
John J. Dillon ◽  
Fernando C. Fervenza
Keyword(s):  
Complement Factor ◽  
C3 Glomerulonephritis ◽  
Factor B ◽  
Complement Factor B

scholarly journals The Association Between Complement Component 2/Complement Factor B Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

2012 ◽  
Vol 176 (5) ◽  
pp. 361-372 ◽  
Author(s):  
Ammarin Thakkinstian ◽  
Mark McEvoy ◽  
Usha Chakravarthy ◽  
Subhabrata Chakrabarti ◽  
Gareth J. McKay ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Meta Analysis ◽  
Complement Component ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B ◽  
Age Related

scholarly journals The purification and properties of the second component of human complement

1978 ◽  
Vol 171 (1) ◽  
pp. 99-107 ◽  
Author(s):  
M A Kerr ◽  
R R Porter
Keyword(s):  
Amino Acid ◽  
Polypeptide Chain ◽  
Alternative Pathway ◽  
Polyacrylamide Gel Electrophoresis ◽  
Complement Factor ◽  
Human Complement ◽  
Terminal Amino Acid ◽  
Factor B ◽  
Antigenic Properties ◽  
Terminal Amino

The second component of human complement (C2) was purified by a combination of euglobulin precipitation, ion-exchange chromatography, (NH4)2SO4 precipitation and affinity chromatography. The final product was homogeneous by the criterion of polyacrylamide-gel electrophoresis and represents a purification of about 4000-fold from serum with 15-20% yield. Component C2 comprises a single carbohydrate-containing polypeptide chain, with an apparent mol.wt. of 102000; alanine is the N-terminal amino acid. The molecule is rapidly cleaved by activated subcomponent C1s with the loss of haemolytic activity to yield two fragments with apparent mol.wts. of 74000 and 34000. These fragments are not linked by disulphide bonds and can be easily separated. A second protein isolated during the purification of component C2 was identified by its haemolytic and antigenic properties as complement Factor B, the protein serving an analogous function to component C2 in the alternative pathway. The protein, which is also a single carbohydrate-containing polypeptide chain, has an apparent mol.wt. of 95000 and threonine as N-terminal amino acid. The amino acid analyses of component C2 and Factor B are compared.

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