scholarly journals The thiol groups of mouse immunoglobulin A. Incomplete formation of the Cα 1-domain disulphide bridge

1985 ◽  
Vol 225 (1) ◽  
pp. 113-125 ◽  
Author(s):  
S A Cockle ◽  
N M Young
Keyword(s):  
High Performance ◽  
Immunoglobulin A ◽  
Secretory Component ◽  
Reduced Form ◽  
Thiol Groups ◽  
Disulphide Bridge ◽  
Myeloma Protein ◽  
Sh Groups ◽  
Heavy Chains ◽  
Bond Model

The BALB/c IgA (immunoglobulin A) myeloma protein M167 contained on average 5.7 free SH groups per IgA dimer. These groups were preponderantly on the heavy chains and comprised two distinct populations: 3.3 exposed SH groups per dimer in the Fc region, and 2.4 buried SH groups per dimer in the Fd region, detectable o only after denaturation. To locate the cysteine residues involved, labelled peptides were purified from thermolysin digests of radioalkylated IgA by high-performance liquid chromatography. From the amino acid compositions of the peptides, the exposed thiol groups were assigned to Cys-307 in the C alpha 2 domain, which thus existed in the reduced form to an extent exceeding 80%. This residue may allow attachment of secretory component to dimer IgA in the mouse to proceed via thiol-disulphide exchange. The buried thiol groups were assigned to Cys-150 and Cys-208, in the C alpha 1 domain, each being in the reduced form to the extent of approx. 30%. This pair of residues would normally give rise to the characteristic intradomain disulphide bridge. It appears that disulphide formation is not a crucial event during folding of the C alpha 1 domain in IgA biosynthesis. The sequence in the region 140-151 was re-investigated, and residue 142 was shown to be serine, not cysteine, helping explain the lack of heavy-chain-light chain bonding in BALB/c mouse IgA. A disulphide-bond model for mouse IgA is proposed on the basis of these assignments and other features of the mouse alpha-chain sequence.

scholarly journals 3D Structures of IgA, IgM, and Components

2021 ◽  
Vol 22 (23) ◽  
pp. 12776
Author(s):  
Shunli Pan ◽  
Noriyoshi Manabe ◽  
Yoshiki Yamaguchi
Keyword(s):  
Structure Function ◽  
Structural Information ◽  
Immunoglobulin A ◽  
Structural Complexity ◽  
Secretory Component ◽  
Immunoglobulin M ◽  
Atomic Scale ◽  
3D Structures ◽  
Heavy Chains ◽  
Effective Option

Immunoglobulin G (IgG) is currently the most studied immunoglobin class and is frequently used in antibody therapeutics in which its beneficial effector functions are exploited. IgG is composed of two heavy chains and two light chains, forming the basic antibody monomeric unit. In contrast, immunoglobulin A (IgA) and immunoglobulin M (IgM) are usually assembled into dimers or pentamers with the contribution of joining (J)-chains, which bind to the secretory component (SC) of the polymeric Ig receptor (pIgR) and are transported to the mucosal surface. IgA and IgM play a pivotal role in various immune responses, especially in mucosal immunity. Due to their structural complexity, 3D structural study of these molecules at atomic scale has been slow. With the emergence of cryo-EM and X-ray crystallographic techniques and the growing interest in the structure-function relationships of IgA and IgM, atomic-scale structural information on IgA-Fc and IgM-Fc has been accumulating. Here, we examine the 3D structures of IgA and IgM, including the J-chain and SC. Disulfide bridging and N-glycosylation on these molecules are also summarized. With the increasing information of structure–function relationships, IgA- and IgM-based monoclonal antibodies will be an effective option in the therapeutic field.

Effect of Vernonia cognata on oxidative damage induced by ethanol in rats

2010 ◽  
Vol 30 (7) ◽  
pp. 675-684 ◽  
Author(s):  
CS Mota ◽  
RB Freitas ◽  
ML Athayde ◽  
AA Boligon ◽  
PR Augusti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Performance ◽  
Tissue Injury ◽  
Antioxidant Effect ◽  
Gastric Tissue ◽  
Thiol Groups ◽  
Protein Thiol ◽  
Stress Markers ◽  
Hydroethanolic Extract ◽  
And Oxidative Stress

Free radicals production and oxidative stress play a central role in injuries caused by ethanol (EtOH) on gastric mucosal. Thus, strategies to counteract EtOH toxicity are highly desirable. This study was aimed at evaluating whether Vernonia cognata extract would reduce EtOH effects in rats. Rats received Vernonia cognata extract (0, 1 and 2 g/kg bw, by gavage) 1 hour after EtOH had been administered (0 or 70%, 0.5 mL/100 g bw, by gavage) and were killed 1 hour after Vernonia cognata extract administration. The stomach was removed for macroscopic and histopathological evaluation, as well as, oxidative stress markers such as lipoperoxidation (LPO) and non-protein thiol groups (NPSH) levels and catalase (CAT) activity. EtOH acute exposure increased LPO and decreased NPSH levels and CAT activity along with macroscopic and microscopic lesions in gastric tissue, confirming the involvement of oxidative stress in EtOH toxicity. Vernonia cognata extract attenuated oxidative and histopathological features induced by EtOH at all evaluated doses. Moreover, both studied doses of Vernonia cognata extract caused an increase in NPSH levels per se. However, only the dose of 2 g/kg reverted all macroscopic changes caused by EtOH toxicity. The protective effect of the extract could be attributed to antioxidant molecules present in the extract, such as flavonoids and phenolic acids, which were quantified by high performance liquid chromatography (HPLC). Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. Our results indicate that Vernonia cognata hydroethanolic extract could have a beneficial role against EtOH toxicity by preventing oxidative stress and gastric tissue injury.

Structure of immunoglobulin A. Cysteine-containing peptides of the α chain of an immunoglobulin A1 myeloma protein

Biochemistry ◽  
1973 ◽  
Vol 12 (25) ◽  
pp. 5186-5194 ◽  
Author(s):  
Enrique Mendez ◽  
Blas Frangione ◽  
Edward C. Franklin
Keyword(s):  
Immunoglobulin A ◽  
Myeloma Protein ◽  
Α Chain

scholarly journals Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin

2020 ◽  
Author(s):  
Yuxin Wang ◽  
Guopeng Wang ◽  
Yaxin Li ◽  
Hao Shen ◽  
Huarui Chu ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Immunoglobulin A ◽  
Underlying Mechanism ◽  
Secretory Component ◽  
Secretory Immunoglobulin A ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Cryo Electron Microscopy ◽  
Structural Insights ◽  
Secretory Immunoglobulin

AbstractSecretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. SIgA possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. The underlying mechanism of how the J-chain and pIgR/SC facilitates the assembly and secretion of SIgA remains to be understood. During the infection of Streptococcus pneumoniae, a pneumococcal adhesin SpsA hijacks SIgA and unliganded pIgR/SC to evade host defense and gain entry to human cells. How SpsA specifically targets SIgA and pIgR/SC also remains unclear. Here we report a cryo-electron microscopy structure of the Fc region of human IgA1 (Fcα) in complex with J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present the structure of Fcα-J-SC in complex with SpsA, which uncovers the specific interaction between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on the pathogenesis of S. pneumoniae.

scholarly journals Biosynthesis of immunoglobulin A (IgA). Secretion and addition of carbohydrate to monomer and polymer forms of a mouse myeloma protein

1973 ◽  
Vol 136 (3) ◽  
pp. 589-596 ◽  
Author(s):  
E. Della Corte ◽  
R. M. E. Parkhouse
Keyword(s):  
Plasma Cell ◽  
Molecular Species ◽  
Specific Antibody ◽  
Early Stage ◽  
Immunoglobulin A ◽  
Carbohydrate Composition ◽  
Myeloma Protein ◽  
J Chain ◽  
Co Precipitation ◽  
Mouse Myeloma

Cell suspensions of mouse plasma-cell tumour MOPC 315 secreting predominantly IgA (immunoglobulin A) monomer and dimer were incubated with radioactive leucine, mannose, galactose and fucose for various periods of time. The amounts of secreted and intracellular immunoglobulins were measured by co-precipitation with specific antibody, and the molecular species present were assessed by electrophoresis in polyacrylamide gels. Analysis of the secreted myeloma protein demonstrated that monomer and dimer IgA molecules are identical with respect to carbohydrate composition and rate of secretion. Within the cell, the myeloma protein is almost entirely accounted for by monomer units which either leave the cell as such or are polymerized with the addition of J chain close to the time of secretion. The results support the concept of a stepwise addition of carbohydrate residues to IgA immunoglobulin during the process of secretion. Similar patterns of carbohydrate assembly were found for the monomer or dimer molecules. Mannose residues are added at an early stage, whereas fucose is added close to the time of secretion. Galactose is also added early, but some may also be incorporated at a later stage. Control of IgA polymerization is considered unlikely to reflect regulation at the level of carbohydrate addition, and it is suggested that the critical controlling factor is the J chain.

Optimized TSV Module for High Performance 2.5D Device Packaging

2014 ◽  
Vol 2014 (DPC) ◽  
pp. 000737-000767
Author(s):  
Cyprian Uzoh ◽  
Liang Wang ◽  
Zhuowen Sun ◽  
Andrew Cao ◽  
Bong-Sub Lee ◽  
...  
Keyword(s):  
Barrier Layer ◽  
High Performance ◽  
Impurity Content ◽  
Electrical Performance ◽  
Reduced Form ◽  
Sidewall Roughness ◽  
Factors Affecting ◽  
Wide Range ◽  
Silicon Vias ◽  
Module Development

3D-IC has been increasingly adopted by the industry owing to its promise of higher device speed and package bandwidth, improved power consumption, reduced form factor, and lower cost for important applications over a wide range of industrial segments including image sensors, logic-memory and logic-logic integration, MEMS, integrated optical interposers and LEDs. This presentation is a systematic study of multiple experimental factors affecting the electrical performance, reliability and scalability of TSVs. Electrical modeling and simulation was used to determine the key factors influencing singal transmission and return losses in TSVs at high (>1 GHz) frequencies. A variety of process modules and steps for the fabrication of through silicon vias were then systematically optimized to ensure high performance. The modules evaluated include TSV etch, TSV fill, chemical mechanical polishing (CMP), pad finish, bonding schemes, wafer thinning, via reveal, passivation, wiring and bumping. One example is the improvement of TSV profile and sidewall roughness through the optimization of DRIE parameters and wet chemical methods to reduce silicon sidewall roughness from that of a typical Bosch etch to less than 10nm which is critical for adhesion of barrier/seed layer and the final reliability of 2.5D packaging. Scalability of void-free via fill process with respect to TSV diameter and depth was addressed by using highly conformal barrier layers. Adhesion of Cu to the barrier layer was also improved upon detailed analysis to prevent delamination and improve reliability. A bottom up plating chemistry with significantly low impurity content was utilized to mitigate voids, seams and excessive overburden in the TSV. Its impact on stress and delamination issues and subsequent reliability failures was studied in details. The annealing process following TSV formation is systematically studied with varying conditions and characterized with metrology and electrical tests to investigate its effect on microstructure and material properties. The process parameters were tuned for CMP of Cu, adhesion and barrier layer without causing corrosion or delamination between adjacent layers. Process requirements for these modules in TSV process are closely related. This presentation will review the process module development in the context of their effects on the integrated TSV parameters (performance, reliability and scalability). We will also provide an in-depth discussion on process module optimization, electrical and mechanical characterization and cost reduction methodologies.

Secretory Immunoglobulin a in Oral and Respiratory Passages in Man

1975 ◽  
Vol 84 (20_suppl) ◽  
pp. 1-23 ◽  
Author(s):  
Goro Mogi
Keyword(s):  
Immunoglobulin A ◽  
Secretory Component ◽  
Secretory Iga ◽  
Secretory Cells ◽  
Antigenic Relationship ◽  
Serum Iga ◽  
Human Colostrum ◽  
Specific Antisera ◽  
Antigenic Relationships ◽  
Secretory Immunoglobulin

Secretory IgA (SIgA) is the predominant immunoglobulin in certain external secretions and may have an important role in immunological mucosal resistance. SIgA differs in chemical and immunological properties from serum IgA. The present study was undertaken to investigate the antigenic relationship between SIgA, free secretory component (FSC) and serum IgA and the localization of SIgA as well as other immunological classes in tissues of oral and respiratory passages by use of immunofluorescence technique. SIgA and FSC were highly purified from human colostrum and rabbit anti-SIgA and anti-SC antisera were prepared. On the basis of antigenic relationships between SIgA, FSC and serum IgA, it was emphasized that individual specific antisera for SC and IgA and/or SIgA should be used in immunochemical or immunohistological investigations for SIgA. The present study failed to detect SC determinants in palatine and lingual tonsils. However, it was evident that cells present in the pharyngeal tonsillar epithelium contain SC determinants. SC molecules may be synthesized in certain secretory cells of mucous membrane and glandular epithelium and the combining of SC with IgA could occur in the cytoplasm of epithelial cells, the intercellular spaces and/or in the lumens of glandular acini and ductules.

Column enzyme immunoassay for secretory immunoglobulin A in serum.

1983 ◽  
Vol 29 (1) ◽  
pp. 151-153 ◽  
Author(s):  
R Yamamoto ◽  
S Kimura ◽  
S Hattori ◽  
Y Ishiguro ◽  
K Kato
Keyword(s):  
Enzyme Immunoassay ◽  
Sodium Carbonate Solution ◽  
Solid Phase ◽  
Immunoglobulin A ◽  
Enzyme Reaction ◽  
Secretory Component ◽  
Secretory Immunoglobulin A ◽  
Serum Samples ◽  
Sepharose 4B ◽  
Secretory Immunoglobulin

Abstract This enzyme immunoassay for specific measurement of secretory immunoglobulin A concentrations in human serum involves use of a small chromatographic column as a solid-phase. Serum samples are incubated for 2 h with beta-D-galactosidase-labeled antibody to secretory component, then passed through a 0.1-mL Sepharose 4B column containing antibodies to human immunoglobulin A. After the column is washed to remove the unbound label, the buffer in the column is replaced by a solution of o-nitrophenyl-beta-D-galactoside (a beta-D-galactosidase substrate) and incubated at 25 degrees C overnight. The enzyme reaction is stopped by washing the column with sodium carbonate solution, and the absorbance of the eluate is measured at 420 nm. The concentration of secretory immunoglobulin A can be determined with a minimum detectable sensitivity of 3 mg/L, without interference from free immunoglobulin A and secretory component in the same samples.

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