GAG positioning on IL-1RI; A mechanism regulated by dual effect of glycosylation

SARS-CoV-2 is a strain of Coronavirus family that caused the ongoing pandemic of COVID-19. Several studies showed that the glycosylation of virus spike (S) protein and the Angiotensin-Converting Enzyme 2 (ACE2) receptor on the host cell is critical for the virus infectivity. Molecular Dynamics (MD) simulations were used to explore the role of a novel mutated O-glycosylation site (D494S) on the Receptor Binding Domain (RBD) of S protein. This site was suggested as a key mediator of virus-host interaction. By exploring the dynamics of three O-glycosylated models and the control systems of unglcosylated S4944 and S494D complexes, it was shown that the decoration of S494 with elongated O-glycans results in stabilized interactions on the direct RBD-ACE2. Calculation of the distances between RBD and two major H1, H2 helices of ACE2 and the interacting pairs of amino acids in the interface showed that the elongated O-glycan maintains these interactions by forming several polar contacts with the neighbouring residues while it would not interfere in the direct binding interface. Relative binding free energy of RBD-ACE2 is also more favorable in the O-glycosylated models with longer glycans. The increase of RBD binding affinity to ACE2 depends on the size of attached O-glycan. By increasing the size of O-glycan, the RBD-ACE2 binding affinity will increase. Hence, this crucial factor must be taken into account for any further inhibitory approaches towards RBD-ACE2 interaction.

show abstract

“…11 ). The increase of the binding free energy in the glycosylated protein-ligand complexes are also reported in other studies 39 , 47 .…”

Section: Resultssupporting

confidence: 85%

S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study

Rahnama

Irani

Amininasab

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…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%

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

Nomandan

Irani

Hosseini

2022

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…We highlight case studies of cytokines with emerging diverse roles, while also showcasing experimental and theoretical approaches for understanding cytokine biochemistry. Though we cannot comprehensively discuss every avenue of investigation in this Review ( Künze et al, 2014 ; Herring et al, 2015 ; Joseph et al, 2015 ; Künze et al, 2016 ; Park et al, 2017 ; Azimzadeh Irani and Ejtehadi, 2019 ; Penk et al, 2019 ; Gangele et al, 2020 ; Roy, 2020 ; Yang, 2020 ), each of the case studies below offers a useful piece insight into an extremely complex class of biomolecules that may aid in the development of broadly applicable strategies to study molecular interactions.…”

Section: Introductionmentioning

confidence: 99%

Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function

Cui

Lisi

2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Cytokines are key mediators of cellular communication and regulators of biological advents. The timing, quantity and localization of cytokines are key features in producing specific biological outcomes, and thus have been thoroughly studied and reviewed while continuing to be a focus of the cytokine biology community. Due to the complexity of cellular signaling and multitude of factors that can affect signaling outcomes, systemic level studies of cytokines are ongoing. Despite their small size, cytokines can exhibit structurally promiscuous and dynamic behavior that plays an equally important role in biological activity. In this review using case studies, we highlight the recent insight gained from observing cytokines through a molecular lens and how this may complement a system-level understanding of cytokine biology, explain diversity of downstream signaling events, and inform therapeutic and experimental development.

show abstract

GAG positioning on IL-1RI; A mechanism regulated by dual effect of glycosylation

Cited by 8 publications

References 61 publications

S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study

S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study

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

Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function

Contact Info

Product

Resources

About