Abundance and Stability as Common Properties of Allergens

Frontiers in Allergy ◽

10.3389/falgy.2021.769728 ◽

2021 ◽

Vol 2 ◽

Author(s):

Alexander C. Y. Foo ◽

Geoffrey A. Mueller

Keyword(s):

Immune System ◽

Protein Stability ◽

Allergic Disease ◽

Human Exposure ◽

Statistical Analyses ◽

Biophysical Properties ◽

Epidemiological Surveys ◽

Exposure Levels ◽

The Stability

There have been many attempts to identify common biophysical properties which differentiate allergens from their non-immunogenic counterparts. This review will focus on recent studies which examine two such factors: abundance and stability. Anecdotal accounts have speculated that the elevated abundance of potential allergens would increase the likelihood of human exposure and thus the probability of sensitization. Similarly, the stability of potential allergens dictates its ability to remain a viable immunogen during the transfer from the source to humans. This stability could also increase the resilience of potential allergens to both gastric and endosomal degradation, further skewing the immune system toward allergy. Statistical analyses confirm both abundance and stability as common properties of allergens, while epidemiological surveys show a correlation between exposure levels (abundance) and allergic disease. Additional studies show that changes in protein stability can predictably alter gastric/endosomal processing and immunogenicity, providing a mechanistic link between stability and allergenicity. However, notable exceptions exist to both hypotheses which highlight the multifaceted nature of immunological sensitization, and further inform our understanding of some of these other factors and their contribution to allergic disease.

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Applicability of Instability Index for In vitro Protein Stability Prediction

Protein and Peptide Letters ◽

10.2174/0929866526666190228144219 ◽

2019 ◽

Vol 26 (5) ◽

pp. 339-347 ◽

Cited By ~ 4

Author(s):

Dilani G. Gamage ◽

Ajith Gunaratne ◽

Gopal R. Periyannan ◽

Timothy G. Russell

Keyword(s):

Protein Stability ◽

Caulobacter Crescentus ◽

Effect Of Temperature ◽

Instability Index ◽

Dipeptide Composition ◽

Experimental Conditions ◽

The Stability ◽

Vitro Protein

Background: The dipeptide composition-based Instability Index (II) is one of the protein primary structure-dependent methods available for in vivo protein stability predictions. As per this method, proteins with II value below 40 are stable proteins. Intracellular protein stability principles guided the original development of the II method. However, the use of the II method for in vitro protein stability predictions raises questions about the validity of applying the II method under experimental conditions that are different from the in vivo setting. Objective: The aim of this study is to experimentally test the validity of the use of II as an in vitro protein stability predictor. Methods: A representative protein CCM (CCM - Caulobacter crescentus metalloprotein) that rapidly degrades under in vitro conditions was used to probe the dipeptide sequence-dependent degradation properties of CCM by generating CCM mutants to represent stable and unstable II values. A comparative degradation analysis was carried out under in vitro conditions using wildtype CCM, CCM mutants and two other candidate proteins: metallo-β-lactamase L1 and α -S1- casein representing stable, borderline stable/unstable, and unstable proteins as per the II predictions. The effect of temperature and a protein stabilizing agent on CCM degradation was also tested. Results: Data support the dipeptide composition-dependent protein stability/instability in wt-CCM and mutants as predicted by the II method under in vitro conditions. However, the II failed to accurately represent the stability of other tested proteins. Data indicate the influence of protein environmental factors on the autoproteolysis of proteins. Conclusion: Broader application of the II method for the prediction of protein stability under in vitro conditions is questionable as the stability of the protein may be dependent not only on the intrinsic nature of the protein but also on the conditions of the protein milieu.

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Cell-Penetrating Peptide-Mediated Nanovaccine Delivery

Current Drug Targets ◽

10.2174/1389450122666210203193225 ◽

2021 ◽

Vol 22 ◽

Author(s):

Jizong Jiang

Keyword(s):

Immune System ◽

Immune Responses ◽

Cell Penetrating Peptide ◽

Antigen Delivery ◽

Efficient Manner ◽

Antigen Uptake ◽

Cell Penetrating ◽

The Stability ◽

Antigen Presenting

Abstract: Vaccination with small antigens, such as proteins, peptides, or nucleic acids, is used to activate the immune system and trigger the protective immune responses against a pathogen. Currently, nanovaccines are undergoing development instead of conventional vaccines. The size of nanovaccines is in the range of 10–500 nm, which enables them to be readily taken up by cells and exhibit improved safety profiles. However, low-level immune responses, as the removal of redundant pathogens, trigger counter-effective activation of the immune system invalidly and present a challenging obstacle to antigen recognition and its uptake via antigen-presenting cells (APCs). In addition, toxicity can be substantial. To overcome these problems, a variety of cell-penetrating peptide (CPP)-mediated vaccine delivery systems based on nanotechnology have been proposed, most of which are designed to improve the stability of antigens in vivo and their delivery into immune cells. CPPs are particularly attractive components of antigen delivery. Thus, the unique translocation property of CPPs ensures that they remain an attractive carrier with the capacity to deliver cargo in an efficient manner for the application of drugs, gene transfer, protein, and DNA/RNA vaccination delivery. CPP-mediated nanovaccines can enhance antigen uptake, processing, and presentation by APCs, which are the fundamental steps in initiating an immune response. This review describes the different types of CPP-based nanovaccines delivery strategies.

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A glycine-specific N-degron pathway mediates the quality control of protein N-myristoylation

Science ◽

10.1126/science.aaw4912 ◽

2019 ◽

Vol 365 (6448) ◽

pp. eaaw4912 ◽

Cited By ~ 27

Author(s):

Richard T. Timms ◽

Zhiqian Zhang ◽

David Y. Rhee ◽

J. Wade Harper ◽

Itay Koren ◽

...

Keyword(s):

Quality Control ◽

Protein Stability ◽

Protein Degradation ◽

E3 Ligase ◽

Cleavage Sites ◽

Caspase Cleavage ◽

E3 Ligases ◽

Ring E3 Ligase ◽

The Stability ◽

Ring E3

The N-terminal residue influences protein stability through N-degron pathways. We used stability profiling of the human N-terminome to uncover multiple additional features of N-degron pathways. In addition to uncovering extended specificities of UBR E3 ligases, we characterized two related Cullin-RING E3 ligase complexes, Cul2ZYG11B and Cul2ZER1, that act redundantly to target N-terminal glycine. N-terminal glycine degrons are depleted at native N-termini but strongly enriched at caspase cleavage sites, suggesting roles for the substrate adaptors ZYG11B and ZER1 in protein degradation during apoptosis. Furthermore, ZYG11B and ZER1 were found to participate in the quality control of N-myristoylated proteins, in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation. Thus, an additional N-degron pathway specific for glycine regulates the stability of metazoan proteomes.

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Antagonistic Control of Disease Resistance Protein Stability in the Plant Immune System

Science ◽

10.1126/science.1109977 ◽

2005 ◽

Vol 309 (5736) ◽

pp. 929-932 ◽

Cited By ~ 165

Author(s):

B. F. Holt

Keyword(s):

Disease Resistance ◽

Immune System ◽

Protein Stability ◽

Plant Immune System ◽

Disease Resistance Protein ◽

Resistance Protein ◽

Antagonistic Control

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Hopf Bifurcation Induced by Delay Effect in a Diffusive Tumor-Immune System

International Journal of Bifurcation and Chaos ◽

10.1142/s0218127418501365 ◽

2018 ◽

Vol 28 (11) ◽

pp. 1850136 ◽

Cited By ~ 1

Author(s):

Ben Niu ◽

Yuxiao Guo ◽

Yanfei Du

Keyword(s):

Immune System ◽

Hopf Bifurcation ◽

Periodic Solutions ◽

Center Manifold ◽

Immune Cell ◽

Tumor Treatment ◽

Delay Effect ◽

Stable Periodic ◽

The Stability ◽

Bifurcation And Stability

Tumor-immune interaction plays an important role in the tumor treatment. We analyze the stability of steady states in a diffusive tumor-immune model with response and proliferation delay [Formula: see text] of immune system where the immune cell has a probability [Formula: see text] in killing tumor cells. We find increasing time delay [Formula: see text] destabilizes the positive steady state and induces Hopf bifurcations. The criticality of Hopf bifurcation is investigated by deriving normal forms on the center manifold, then the direction of bifurcation and stability of bifurcating periodic solutions are determined. Using a group of parameters to simulate the system, stable periodic solutions are found near the Hopf bifurcation. The effect of killing probability [Formula: see text] on Hopf bifurcation values is also discussed.

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Cellular ATP Levels Determine the Stability of a Nucleotide Kinase

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.790304 ◽

2021 ◽

Vol 8 ◽

Author(s):

Oliver Brylski ◽

Puja Shrestha ◽

Patricia Gnutt ◽

David Gnutt ◽

Jonathan Wolf Mueller ◽

...

Keyword(s):

Protein Stability ◽

Bound States ◽

Atp Depletion ◽

Aps Kinase ◽

Cellular Processes ◽

Atp Levels ◽

Stability Change ◽

Cell Stability ◽

The Stability ◽

Nucleotide Kinase

The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.

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Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.17.54 ◽

2021 ◽

Vol 17 ◽

pp. 622-629

Author(s):

Naohiro Horie ◽

Takao Yamaguchi ◽

Shinji Kumagai ◽

Satoshi Obika

Keyword(s):

Nucleic Acid ◽

Binding Affinity ◽

Antisense Oligonucleotides ◽

Modified Oligonucleotides ◽

Biophysical Properties ◽

Chemical Modifications ◽

Antisense Technology ◽

Strong Affinity ◽

The Stability

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (mC). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

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Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg reconstitution and stabilizing Foxp3 expression

Blood ◽

10.1182/blood-2016-02-698241 ◽

2016 ◽

Vol 128 (16) ◽

pp. 2068-2082 ◽

Cited By ~ 20

Author(s):

Ludovic Belle ◽

Kimberle Agle ◽

Vivian Zhou ◽

Cheng Yin-Yuan ◽

Richard Komorowski ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

Regulatory T Cells ◽

Foxp3 Expression ◽

Interleukin 27 ◽

Key Points ◽

The Stability

Key Points Blockade of IL-27 signaling mitigates the severity of GVHD by recalibrating the effector and regulatory arms of the immune system. Inhibition of IL-27 augments the reconstitution of CD4+ and CD8+ regulatory T cells and increases the stability of Foxp3 expression.

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Research of Immune Controllers

Handbook of Research on Artificial Immune Systems and Natural Computing ◽

10.4018/978-1-60566-310-4.ch013 ◽

2011 ◽

pp. 262-303

Author(s):

Fu Dongmei

Keyword(s):

Control System ◽

Immune System ◽

B Cells ◽

Control Systems ◽

Artificial Immune System ◽

General Structure ◽

Engineering Application ◽

Error Characteristic ◽

Artificial Immune ◽

The Stability

In engineering application, the characteristics of the control system are entirely determined by the system controller once the controlled object has been chosen. Improving the traditional controller or constructing the new controller is an unfading study field of control theory and application. The control system is greatly enriched and developed by this way. As a complicated self-adaptable system, the biological immune system can effectively and smoothly stand against antigens and viruses intruded into organism. It is possible to improve the self-learning, adaptive and robustness capability of the control system through embedded an artificial immune controller in control system. Based on the biological immune mechanism and artificial immune model, this chapter attempts to study the immune controller design and application in traditional control system..First, a kind of artificial immune controller is proposed based on the T-B cells immunity. The boundedness and the stability of SISO control systems, which constructed by the artificial immune controller, are proved by the little gain theorem. A general controller structure frame based on the T-B cells immunity is proposed, which includes the same kind of controller proposed previously. The validity of this artificial immune controller is verified by simulation. Second, a new type of artificial immune controllers is constructed according to a simple double-cell immune dynamics model. The non-error characteristic of SISO control systems, which constructed by the artificial immune controller, is proved by the nonlinear theory in this chapter. The I/O stability and no-error characteristic of the system are verified by simulations, which show that the kind of artificial immune system have good anti-lag capability. Third, the Varela immune network model has been improved based on which an artificial immune system is proposed. The odd linearization method of the non-linear system is used to prove the stability and non-error characteristic of the SISO system constructed by the artificial immune control system. Its I/O stability, non-error characteristic and strong anti-lag capability are also verified by simulation. Finally, based on the comparison of the three kinds of immune controllers, a general structure of the artificial immune controller is proposed. The further study on this field is indicated in this chapter lastly.

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