Glycan-mediated functional assembly of IL-1RI: structural insights into completion of the current description for immune response

Irani, Maryam Azimzadeh; Ejtehadi, Mohammad Reza

doi:10.1080/07391102.2020.1841027

Cited by 6 publications

(2 citation statements)

References 61 publications

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“…At the same time, the presence of additional glycans in the complex of the gmRBD causes ferritin and RBD to stick together like glue ( Figure 11 ). Two previous studies have reported this glue-like function of the glycans in protein–protein interactions ( Azimzadeh Irani and Ejtehadi, 2020 ; Motamedi et al, 2021 ). These observations are consistent with the increased stability of the refined nanoparticle shown in the RMSD, PCA, and secondary structure plots ( Figure 3A , Figure 6 , Figure 9 ).…”

Section: Resultsmentioning

confidence: 60%

“…Glycosylation is the most common posttranslational modification that occurs for the virus, and the SARS-CoV-2 proteins, especially the S protein and its receptor ACE2, are densely glycosylated ( Shajahan et al, 2020 ; Woo et al, 2020 ; Gong et al, 2021 ; Guo et al, 2021 ). In several studies, glycosylation has been shown to be essential for protein folding, stability, and ligand binding ( Azimzadeh Irani et al, 2017 ; Azimzadeh Irani, 2018 ; Azimzadeh Irani and Ejtehadi, 2020 ; Motamedi et al, 2021 ; Rahnama et al, 2021 ). Both N-glycosylation and O-glycosylation occur on the spike protein of SARS-CoV-2, and the latter has a significant effect on virus function and infectivity ( Xu et al, 2020 ; Yasunori et al, 2020 ; Antonopoulos et al, 2021 ; Bagdonaite et al, 2021 ; Reis et al, 2021 ; Zhang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine

Nomandan

Irani

Hosseini

2022

Front. Mol. Biosci.

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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.

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Section: Resultsmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine

Nomandan

Irani

Hosseini

2022

Front. Mol. Biosci.

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Glycosylation promotes the cancer regulator EGFR-ErbB2 heterodimer formation — molecular dynamics study

2021

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Cancer regulator EGFR-ErbB4 heterodimer is stabilized through glycans at the dimeric interface

et al. 2022

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The ErbB family of tyrosine kinase receptors is composed of four homologous members, including EGFR (ErbB1/HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4). Since the ErbB proteins play vital roles in various developmental processes, their mutation or overexpression leads to severe abnormalities such as cancer. The general mechanism of ErbB receptors activity is binding to growth factors via their extracellular domain followed by tyrosine phosphorylation intracellularly. Yet the EGFR and ErbB4 are the only two members that keep their ligand-binding domain and the tyrosine kinase activated. In contrast, ErbB2 and ErbB3 are incapable of keeping their ligand-binding and kinase domains activated, respectively. Active ErbB receptors form homo and heterodimers by binding of two similar or different family members together, respectively. Ligands and intracellular pathways that could be activated through heterodimerization are more diverse compared to homodimers. Moreover, it is known that Nglycosylation is critical for stabilizing and activating the ErbB receptors. In this study, atomistic molecular dynamics simulations were used on one of the most potentiated ErbB heterodimers (EGFR-ErbB4) in the glycosylated and unglycosylated states. It was shown that the EGFR-ErbB4 heterodimer is highly stabilized by glycosylation. The increased stability is most signi cant at the dimeric interfaces. Regulated by packing of three glycans attached to EGFR (Asn337) and ErbB4 (Asn333, Asn523) at the dimeric interface. Finally, it is proposed that heterodimerization is the persistent key player of the ErbB receptors activation. Thus, targeting the heterodimers in future therapeutic designs could be a promising approach against drug resistance ErbB positive cancers.

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Glycan-mediated functional assembly of IL-1RI: structural insights into completion of the current description for immune response

Cited by 6 publications

References 61 publications

In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine

In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine

Glycosylation promotes the cancer regulator EGFR-ErbB2 heterodimer formation — molecular dynamics study

Cancer regulator EGFR-ErbB4 heterodimer is stabilized through glycans at the dimeric interface

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