19 results on '"Azimzadeh Irani, Maryam"'
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2. Metabolomics analysis of milk thistle lipids to identify drought-tolerant genes
- Author
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Ghanbari Moheb Seraj, Rahele, Tohidfar, Masoud, Azimzadeh Irani, Maryam, Esmaeilzadeh-Salestani, Keyvan, Moradian, Toktam, Ahmadikhah, Asadollah, and Behnamian, Mahdi
- Published
- 2022
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3. Cancer regulator EGFR-ErbB4 heterodimer is stabilized through glycans at the dimeric interface
- Author
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Motamedi, Zahra, Shahsavari, Mehri, Rajabi-Maham, Hassan, and Azimzadeh Irani, Maryam
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- 2022
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4. Glycosylation promotes the cancer regulator EGFR-ErbB2 heterodimer formation — molecular dynamics study
- Author
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Motamedi, Zahra, Rajabi-Maham, Hassan, and Azimzadeh Irani, Maryam
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- 2021
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5. Identification of the key functional genes in salt-stress tolerance of Cyanobacterium Phormidium tenue using in silico analysis
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Shahbazi, Mehrdad, Tohidfar, Masoud, and Azimzadeh Irani, Maryam
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- 2021
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6. S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study
- Author
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Rahnama, Shadi, Azimzadeh Irani, Maryam, Amininasab, Mehriar, and Ejtehadi, Mohammad Reza
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- 2021
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7. Molecular mechanism of glycosylated IL-1RII counteraction with IL-1RI in regulation of the immune response.
- Author
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Jamshidi Khameneh, Narges, Azimzadeh Irani, Maryam, and Ejtehadi, Mohammad Reza
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IMMUNOREGULATION , *INTERLEUKIN-1 receptors , *LIGAND binding (Biochemistry) , *CELLULAR signal transduction - Abstract
Interleukin-1 Receptor Type II (IL-1RII) is the decoy receptor of IL-1 cytokines. It down-regulates the immune signalling pathways. There is a competitive behaviour between the IL-1RII and IL-1RI, which is the signalling receptor of the IL-1Rs family. By adopting similarities in structure and specific shared ligands, the two receptors are competing regulators of the immune response. Conformational changes of IL-1RII is a crucial factor in its ligand binding and activation. In addition, dynamics and functionality of the receptor are known to be regulated by glycosylation. Herein, all-atom Molecular Dynamics (MD) simulations were carried out to investigate the dynamics of the apo and cytokine-bound IL-1RII upon full glycosylation. Simulations showed that the IL-1RII presents two extended/active and compact/inactive conformations. Glycosylation maintains the conformation in the extended/active state. Furthermore, It was shown that IL-1 cytokine binding to IL-1RII contributes to stabilisation of the receptor. Comparison of IL-1RI and IL-1RII interaction with IL-1β at the equilibrium condition predicted that glycosylation could increase the binding possibility of IL-1RII towards its ligand. That supports preservation of the active/extended conformation by glycosylation as observed in MD simulations. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Glycan-mediated functional assembly of IL-1RI: structural insights into completion of the current description for immune response.
- Author
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Azimzadeh Irani, Maryam and Ejtehadi, Mohammad Reza
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- 2022
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9. Role of glycosylation in EGFR ectodomain interactions : a molecular dynamics study
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Azimzadeh Irani, Maryam, Chandra Shekhar Verma, and School of Biological Sciences
- Subjects
Science::Biological sciences [DRNTU] - Abstract
The Epidermal Growth Factor Receptor (EGFR) is a tyrosine kinase protein, overexpressed in several cancers. The extracellular domain of EGFR is heavily glycosylated with sugar moieties of varying compositions. Growth factor (mostly Epidermal Growth Factor or EGF) binding activates EGFR. This occurs by inducing the transition from the autoinhibited tethered conformation to an extended conformation of the monomeric form of EGFR and by stabilizing the flexible pre-formed dimer. Several antibodies inhibit EGFR by targeting the growth factor binding site or the dimeric interfaces. Activated EGFR adopts a back-to-back dimeric conformation after binding of another homologous receptor to its extracellular domain as the dimeric partner. Atomistic MD simulations show that glycosylation of the EGFR extracellular domain play critical roles in the binding of growth factors, monoclonal antibodies and the dimeric partners to the monomeric EGFR extracellular domain. N-glycosylation favors growth factor binding to EGFR by a combinatorial mechanism of hydrogen bonding, non-bonded interactions and several intramolecular contacts. Glycosylation also plays distinct roles in binding of antibodies to spatially separated epitopes of the EGFR extracellular domain and assist in maintaining the dimeric interfaces. In the activation process of EGFR, N-glycosylation reduces the flexibility of the tethered and extended monomeric forms of EGFR extracellular domain. By supporting the glycosylated form of the extended state and weakening the tethering interactions in the tethered state, glycosylation supports the extended conformation and facilitates the tethered-extended transition. Dimerization of the EGFR extracellular domain is regulated by attached N-glycans which decrease the flexibility of the dimeric conformation. The decrease in flexibility results in increases in intramonomeric turn motions and intradimeric twist motions which likely induces the asymmetric arrangements of the transmembrane and subsequently the intracellular kinase domains which triggers the signaling cascade in the cystosol. Doctor of Philosophy (SBS)
- Published
- 2017
10. Correlation between experimentally indicated and atomistically simulated roles of EGFR N-glycosylation*.
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Azimzadeh Irani, Maryam
- Subjects
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GLYCOSYLATION , *EPIDERMAL growth factor receptors , *MOLECULAR dynamics , *PROTEIN-tyrosine kinases , *HYDROGEN bonding , *STATISTICAL correlation - Abstract
Epidermal Growth Factor Receptor (EGFR) is a glycosylated tyrosine kinase receptor associated with several cancers. EGFR plays an important role in cancer therapy and inspired several experimental and computational (molecular dynamics simulation) studies to investigate its function and dynamics. N-glycosylation is a critical aspect of EGFR functioning that was mainly unexplained until recently due to the challenges in obtaining and analysis of the structural data involving the glycan moieties. Latest simulations of glycosylated EGFR suggest atomistic mechanisms underlying the experimentally proposed functions of N-glycans in: EGFR increased ligand binding, reduced flexibility and arrangement within the cell membrane. It was shown that the increase in the ligand binding of glycosylated EGFR is mediated by the interaction between the two glycans attached to the growth factor binding subdomains resulting in stabilization of the growth factor binding site. Persistent hydrogen bonds’ formation between the glycans and EGFR contributes to proper folding and reduced flexibly of the glycosylated receptor. Assembly of the cell-integrated EGFR and its relative distance from the membrane are acquired by the lift-up action of the attached glycans. These findings can be used as a framework for implementation of computational techniques to obtain atomistic details of protein glycosylation as one of the most important areas of structural biology. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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11. Correlation between experimentally indicated and atomistically simulated roles of EGFR N-glycosylation*.
- Author
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Azimzadeh Irani, Maryam
- Subjects
GLYCOSYLATION ,EPIDERMAL growth factor receptors ,MOLECULAR dynamics ,PROTEIN-tyrosine kinases ,HYDROGEN bonding ,STATISTICAL correlation - Abstract
Epidermal Growth Factor Receptor (EGFR) is a glycosylated tyrosine kinase receptor associated with several cancers. EGFR plays an important role in cancer therapy and inspired several experimental and computational (molecular dynamics simulation) studies to investigate its function and dynamics. N-glycosylation is a critical aspect of EGFR functioning that was mainly unexplained until recently due to the challenges in obtaining and analysis of the structural data involving the glycan moieties. Latest simulations of glycosylated EGFR suggest atomistic mechanisms underlying the experimentally proposed functions of N-glycans in: EGFR increased ligand binding, reduced flexibility and arrangement within the cell membrane. It was shown that the increase in the ligand binding of glycosylated EGFR is mediated by the interaction between the two glycans attached to the growth factor binding subdomains resulting in stabilization of the growth factor binding site. Persistent hydrogen bonds’ formation between the glycans and EGFR contributes to proper folding and reduced flexibly of the glycosylated receptor. Assembly of the cell-integrated EGFR and its relative distance from the membrane are acquired by the lift-up action of the attached glycans. These findings can be used as a framework for implementation of computational techniques to obtain atomistic details of protein glycosylation as one of the most important areas of structural biology. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Role of N-glycosylation in EGFR ectodomain ligand binding.
- Author
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Azimzadeh Irani, Maryam, Kannan, Srinivasaraghavan, and Verma, Chandra
- Abstract
ABSTRACT The epidermal growth factor receptor (EGFR) is a tyrosine kinase protein, overexpressed in several cancers. The extracellular domain of EGFR is known to be heavily glycosylated. Growth factor (mostly epidermal growth factor or EGF) binding activates EGFR. This occurs by inducing the transition from the autoinhibited tethered conformation to an extended conformation of the monomeric form of EGFR and by stabilizing the flexible preformed dimer. Activated EGFR adopts a back-to-back dimeric conformation after binding of another homologous receptor to its extracellular domain as the dimeric partner. Several antibodies inhibit EGFR by targeting the growth factor binding site or the dimeric interfaces. Glycosylation has been shown to be important for modulating the stability and function of EGFR. Here, atomistic MD simulations show that N-glycosylation of the EGFR extracellular domain plays critical roles in the binding of growth factors, monoclonal antibodies, and the dimeric partners to the monomeric EGFR extracellular domain. N-glycosylation results in the formation of several noncovalent interactions between the glycans and EGFR extracellular domain near the EGF binding site. This stabilizes the growth factor binding site, resulting in stronger interactions (electrostatic) between the growth factor and EGFR. N-glycosylation also helps maintain the dimeric interface and plays distinct roles in binding of antibodies to spatially separated epitopes of the EGFR extracellular domain. Analysis of SNP data suggests the possibility of altered glycosylation with functional consequences. Proteins 2017; 85:1529-1549. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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13. Functional annotation and evaluation of hypothetical proteins in cyanobacterium Synechocystis sp. PCC 6803.
- Author
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Shahbazi, Mehrdad, Tohidfar, Masoud, Azimzadeh Irani, Maryam, and Moheb Seraj, Rahele Ghanbari
- Subjects
INDUSTRIAL microbiology ,SYNECHOCYSTIS ,DNA ,MEMBRANE proteins ,SYNECHOCOCCUS ,ADENOSINE triphosphate - Abstract
The cyanobacterium Synechocystis sp. PCC 6803 is well reported as a potential species for producing valuable bioactive compounds as well as model microorganism for investigating photosynthesis. However, there are a great number of proteins in the genome of this microorganism with unclear functions. To this end, the present study employed numerous bioinformatics techniques in conjunction with experimental validation to describe the function of four hypothetical proteins in cyanobacterium Synechocystis sp. PCC 6803. Four potential proteins, namely sll1388, sll1512 (cytosolic), sll1164, and slr0964 (membrane), were selected for functional annotation. The sll1388 and sll1512 proteins containing adenosine triphosphate (ATP) and deoxyribonucleic acid (DNA) are expected to be induced by toxic concentrations of NaCl and hydrogen peroxide (H 2 O 2). Sll1164 and slr0964 are predicted as membrane proteins involved in cysteine (Cys) and ferrous (Fe
2+ ) transport. The Adaptive Poisson-Boltzmann Solver (APBS) findings suggested negative and positive charges for ligand-binding sites and negative and uncharged residues for predicted pores. Transcript levels of sll1388 and sll1512 increased at high concentrations of NaCl and H 2 O 2. An increase in the expression level of sll1164 and slr0964 was observed under Sulfur (S) and Fe2+ depletion. Transcript analysis along with experimental gene expression research gave us vital indications concerning the function of the above-mentioned hypothetical proteins. The present study used a combination of in silico approaches in conjugation with experimental methods, which finally increased our understanding of the stress tolerance of Synechocystis sp. PCC 6803 as a potential model microorganism with industrial applications. [Display omitted] • The whole-genome encoded hypothetical proteins in Synechocystis sp. PCC 6803 were identified. • Biological network remodeling of sll1164, sll1388, sll1512 and slr0964 proteins was performed. • Physico-chemical properties of selected proteins were calculated. • Protein structure modeling and ligand binding sites of selected proteins were predicted. • Transcript abundance of hypothetical proteins were measured using qRT-PCR. [ABSTRACT FROM AUTHOR]- Published
- 2022
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14. Computational design and investigation of the monomeric spike SARS-CoV-2-ferritin nanocage vaccine stability and interactions.
- Author
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Garmeh Motlagh F, Azimzadeh Irani M, Masoomi Nomandan SZ, and Assadizadeh M
- Abstract
Since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, several solutions have been proposed to manage the disease. The most viable option for controlling this virus is to produce effective vaccines. Most of the current SARS-CoV-2 vaccines have focused on the infusion spike protein. Spike exists as a trimer and plays a vital role in infecting host cells by binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor through its Receptor Binding Domain (RBD). Ferritin protein, a naturally occurring iron-storage protein, has gained attention for vaccine production due to its self-assembling property, non-toxic nature, and biocompatibility. Ferritin nanocages have recently been employed in the development of a SARS-CoV-2 vaccination eliciting not only long-term protective memory cells but also a sustained antibody response. In this study, a combination of in silico investigations including molecular docking, molecular dynamics simulations, and immune simulations were carried out to computationally model the monomeric spike protein on the ferritin nanocage as well as to evaluate its stability and interactions for the first time. The structural dynamics of the modeled complex demonstrated noticeable stability. In particular, the Receptor Binding Domain (RBD) and ferritin within the monomeric spike-ferritin complex illustrated significant stability. The lack of alterations in the secondary structure further supported the overall steadiness of the complex. The decline in the distance between ferritin and spike suggests a strong interaction over time. The cross-correlation matrices revealed that the monomeric spike and ferritin move towards each other supporting the stable interaction between spike and ferritin. Further, the orientation of monomeric spike protein within the ferritin unit facilitated the exposure of critical epitopes, specifically upward active Receptor Binding Domain (RBD), enabling effective interactions with the ACE2 receptor. The immune simulations of the model indicated high-level stimulations of both cellular and humoral immunity in the human body. It was also found that the employed model is effective regardless of the mutated spikes in different variants. These findings shed light on the current status of the SARS-CoV-2-ferritin nanoparticle vaccines and could be used as a framework for other similar vaccine designs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Garmeh Motlagh, Azimzadeh Irani, Masoomi Nomandan and Assadizadeh.)
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- 2024
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15. In-silico structural analysis of Heterocephalus glaber amyloid beta: an anti-Alzheimer's peptide.
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Javanmard A, Azimzadeh-Irani M, Tafazzoli G, Esmaeilzadeh A, Shirinpoor-Kharf M, and Haghayeghi SMH
- Abstract
Heterocephalus glaber , known as the Naked mole-rat, has an extraordinary immunity to Alzheimer's disease. The pathological hallmark of Alzheimer's disease is cerebral accumulations of plaques, consisting of self-aggregated amyloid beta peptides. Homo sapiens and H. glaber amyloid beta peptides are different in only one amino acid. Herein, computational structural analyses were carried out to determine whether plaque development in H. glaber is prevented by the replacement of His13 with Arg13 in the amyloid beta peptide. AlphaFold2 was used to predict the structure of the H. glaber amyloid beta peptide. HADDOCK and Hex were used to self-dock the peptides and dock ions on peptides, respectively. Illustrations were made by PyMol and ChimeraX. Using VMD, we calculated the radius of gyration. The phylogenetic analysis was conducted by Mega. The results showed an accurate structure with two alpha helices separated by a short coil for H. glaber . Self-docking of the two amyloid beta peptides demonstrated a globular conformation in the H. glaber dimer, implying the unlikeliness of amyloid beta peptides' self-aggregation to form fibrillar structures. This conformational state resulted in lower electrostatic energy compared to H. sapiens , contributing to H. glaber's lower tendency for fibril and, ultimately, plaque formation. Phylogenetic analysis confirmed that amyloid precursor protein is highly conserved in each taxon of rodentia and primata. This study provides insight into the connection between the structure of H. glaber amyloid beta and its plaque formation properties, showing that the Arg13 in H. glaber leads to fibril instability, and might prevent senile plaque accumulation., Competing Interests: The authors declare no competing interests.
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- 2024
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16. Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions.
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Assadizadeh M and Azimzadeh Irani M
- Abstract
Introduction: Open Reading Frame 8 (ORF8) is a 121 amino acid length SARS-CoV-2 specific accessory protein that plays crucial roles in viral infectivity, and pathogenesis. Current SARS-CoV-2 treatments focus on spike or RNA-dependent RNA polymerase proteins. Hence, directing attention to ORF8 yields substantial benefits for innovative non-infusional therapeutics. Functional ORF8 is proposed to form oligomers via a crystallographic contact centered by 73YIDI76 motifs. Methods: Hence, the structure and atomistic interactions of trimeric and tetrameric ORF8 oligomeric forms were modeled by means of thorough molecular modeling and molecular dynamics simulations. Results: Results show that trimeric and tetrameric oligomers are stabilized by the interaction of β4-β5 (47-83) loops. 73YIDI76 motifs are involved in obtaining the oligomerization interfaces. It is shown that the tetramers which resemble a doughnut-like construction are the most stabilized oligomeric forms. Where four β4-β5 loops form the interfaces between two dimers. Each monomer links to two others through β4-β5 loops and a covalent Cys20-Cys20 bridge. Epitope mapping, binding site predictions, and solvent-accessible surface area analyses of different ORF8 forms show that the B-cell, MHC-I, and drug epitopes stay exposed in oligomeric forms. Discussion: Approving that the viral infectivity is expanded upon ORF8 oligomerization and the regions involved in oligomerization can be considered as therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Assadizadeh and Azimzadeh Irani.)
- Published
- 2023
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17. Structural arrangement of the active back-to-back dimer in N-glycosylated ErbB receptors is regulated by heterodimerization.
- Author
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Mashayekh-Poul R, Azimzadeh-Irani M, and Masoomi-Nomandan SZ
- Abstract
The human epidermal growth factor receptor (EGFR/ErbB) family consists of four members (ErbB1-4) and belongs to the superfamily of receptor tyrosine kinases (RTKs). The ErbB family members participate in multiple cellular pathways and are the key players in several cancers (brain, breast, lung etc.). Activation of these family members depends on their extracellular domains forming back-to-back hetero/homo dimers. Moreover, dimers are glycosylated, which is a crucial post-translational modification that affects the conformation and function of the protein. Here, molecular modeling and molecular docking are used to comprehensively investigate the dimerization mechanism in glycosylated back-to-back active dimer formation in the entire ErbB receptors for the first time. Results showed that 21 out of 37 clusters of active back-to-back dimers formed by all family members are through heterodimerization. Including; ErbB1-ErbB3/ErbB4, ErbB2-ErbB3/ErbB4 and ErbB3-ErbB4. Ranking ErbB2-ErbB3 as the most stabilized back-to-back dimeric construct. While glycan arrangements favor both homo/hetero dimerization at the dimeric interfaces, it promotes heterodimerization by stabilizing and packing the ligand binding sites of EGFR and ErbB2 respectively. These findings pave the path to future heterodimeric interface/glycan targeting rational anti-cancer drug designs for ErbB receptors., Competing Interests: The authors declare no competing interests.
- Published
- 2023
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18. In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine.
- Author
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Masoomi Nomandan SZ, Azimzadeh Irani M, and Hosseini SM
- Abstract
With the onset of Coronavirus disease 2019 (COVID-19) pandemic, all attention was drawn to finding solutions to cure the coronavirus disease. Among all vaccination strategies, the nanoparticle vaccine has been shown to stimulate the immune system and provide optimal immunity to the virus in a single dose. Ferritin is a reliable self-assembled nanoparticle platform for vaccine production that has already been used in experimental studies. Furthermore, glycosylation plays a crucial role in the design of antibodies and vaccines and is an essential element in developing effective subunit vaccines. In this computational study, ferritin nanoparticles and glycosylation, which are two unique facets of vaccine design, were used to model improved nanoparticle vaccines for the first time. In this regard, molecular modeling and molecular dynamics simulation were carried out to construct three atomistic models of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD)-ferritin nanoparticle vaccine, including unglycosylated, glycosylated, and modified with additional O-glycans at the ferritin-RBD interface. It was shown that the ferritin-RBD complex becomes more stable when glycans are added to the ferritin-RBD interface and optimal performance of this nanoparticle can be achieved. If validated experimentally, these findings could improve the design of nanoparticles against all microbial infections., (Copyright © 2022 Masoomi Nomandan, Azimzadeh Irani and Hosseini.)
- Published
- 2022
- Full Text
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19. GAG positioning on IL-1RI; A mechanism regulated by dual effect of glycosylation.
- Author
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Azimzadeh Irani M and Ejtehadi MR
- Subjects
- Binding Sites, Glycosaminoglycans chemistry, Glycosylation, Humans, Interleukin-1beta chemistry, Interleukin-1beta metabolism, Molecular Dynamics Simulation, Glycosaminoglycans metabolism, Receptors, Interleukin-1 Type I chemistry, Receptors, Interleukin-1 Type I metabolism
- Abstract
IL-1RI is the signaling receptor for the IL-1 family of cytokines that are involved in establishment of the innate and acquired immune systems. Glycosylated extracellular (EC) domain of the IL-1RI binds to agonist such as IL-1β or antagonist ligands and the accessory protein to form the functional signaling complex. Dynamics and ligand binding of the IL-1RI is influenced by presence of the glycosaminoglycans (GAGs) of the EC matrix. Here a combination of molecular dockings and molecular dynamics simulations of the unglycosylated, partially N-glycosylated and fully N-glycosylated IL-1RI EC domain in the apo, GAG-bound and IL-1β-bound states were carried out to explain the co-occurring dynamical effect of receptor's glycosylation and GAGs. It was shown that the IL-1RI adopts two types of "extended" and "locked" conformations in its dynamical pattern, and glycosylation maintains the receptor in the latter form. Maintaining the receptor in the locked conformation disfavors IL-1β binding by burying its two binding site on the IL-1RI EC domain. Glycosylation disfavors GAG binding to the extended IL-1RI EC domain by sterically limiting the GAGs degrees of freedom in targeting its binding site, while it favors GAG binding to the locked IL-1RI by favorable packing interactions., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
- Full Text
- View/download PDF
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