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

Motamedi, Zahra; Rajabi-Maham, Hassan; Irani, Maryam Azimzadeh

doi:10.1007/s00894-021-04986-9

Cited by 8 publications

(4 citation statements)

References 63 publications

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“…The average RMSD values also show that the gmRBDfN system is the most stable. This observation was expected as several other experimental, computational, and structural studies have reported that glycosylation contributes to increasing the stability of protein structures ( Solá and Griebenow, 2009 ; Azimzadeh Irani, 2018 ; Azimzadeh Irani and Ejtehadi, 2019 ; Motamedi et al, 2021 ).…”

Section: Resultssupporting

confidence: 80%

“…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 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: Stabilization Of the Rbd Within The Refined Nanoparticlesupporting

confidence: 88%

“…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: Resultssupporting

confidence: 80%

Section: Stabilization Of the Rbd Within The Refined Nanoparticlesupporting

confidence: 88%

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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“…Recently, presence of bisecting-GlcNAc was shown to also attenuate EGFR signaling and decrease migratory and proliferative potential of breast cancer cells [59]. Finally, in addition to forming homodimers to enable downstream signaling, EGFR is also known to form heterodimers and there are preliminary reports demonstrating that specific glycan-glycan interactions can drive their formation [60]. In fact, recent work has implicated α2,6-sialylated N-glycans of a known dimerization partner of EGFR, human epidermal growth factor receptor 2 (ErbB2/HER2), as a driver of trastuzumab resistance in gastric cancer [61,62].…”

Section: Functional Consequences Of Aberrant Glycosylation At a Prote...mentioning

confidence: 99%

Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics

Čaval¹,

Alisson-Silva²,

Schwarz³

2023

Theranostics

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Cell surface glycosylation has a variety of functions, and its dysregulation in cancer contributes to impaired signaling, metastasis and the evasion of the immune responses. Recently, a number of glycosyltransferases that lead to altered glycosylation have been linked to reduced anti-tumor immune responses: B3GNT3, which is implicated in PD-L1 glycosylation in triple negative breast cancer, FUT8, through fucosylation of B7H3, and B3GNT2, which confers cancer resistance to T cell cytotoxicity. Given the increased appreciation of the relevance of protein glycosylation, there is a critical need for the development of methods that allow for an unbiased interrogation of cell surface glycosylation status.Here we provide an overview of the broad changes in glycosylation at the surface of cancer cell and describe selected examples of receptors with aberrant glycosylation leading to functional changes, with emphasis on immune checkpoint inhibitors, growth-promoting and growth-arresting receptors. Finally, we posit that the field of glycoproteomics has matured to an extent where large-scale profiling of intact glycopeptides from the cell surface is feasible and is poised for discovery of new actionable targets against cancer.

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Glycobiology of Cancer

Vallejo-Ruiz,

Reyes-Leyva

2024

Pathogens Associated With the Development of Cancer in Humans

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

Cited by 8 publications

References 63 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

Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics

Glycobiology of Cancer

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