Study of dephosphorylated 2'-5'-linked oligoadenylates impact on apo-S100A1 protein conformation by heteronuclear NMR and circular dichroism

Abstract

Low molecular weight natural mediators, 2'-5'-linked oligoadenylates, play an important role in interferon-based antiviral mechanism; participate in growth, apoptosis and other important cellular processes. Taking into account their concentration within living cells, the 2'-5'A 3 oligoadenylates may act as additional biologically active substrates, capable of regulating the S100A1 protein functioning in vivo. Aim. Find the evidence for the interaction of human apo-S100A1 with 2'-5'-linked oligoadenylates. Methods. Using the circular dichroism (CD) and heteronuclear NMR spectroscopy. Results. The obtained results demonstrated the occurrence of the secondary structure changes in human S100A1 protein upon the interaction with 2'-5'-linked oligoadenylates as well as indicated specific residues involved in this process. Conclusions. Our study points to the 2'-5'-linked oligoadenylates as possible additional elements of the complex system of fine regulation of the Ca 2+ -signal transduction pathway in human cells.

Complexes of Oligoribonucleotides with D-Mannitol Inhibit Hemagglutinin–Glycan Interaction and Suppress Influenza A Virus H1N1 (A/FM/1/47) Infectivity In Vitro

“…These results suggest that the ORNs- d -M can recognize the viral HA, likely at or around the receptor binding region required for the penetration of the influenza virus into host cells [ 32 ]. Our results also suggest that the ORNs- d -M potentially can bind to amino acids near the glycan binding region [ 2 ], change the conformation of protein [ 11 ], and prevent efficient HA–glycan interaction. To validate the direct virucidal action of the ORNs- d -M in blocking viral binding and entry into the host cells, we evaluated the ability of these complexes to influence cell viability and CPE reduction during the influenza infection.…”

“…They affect proteins of 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway and this manner lead to the destruction of viral RNA [ 31 ]. The 2′-5′-As can bind to the proteins of signaling pathways of innate immunity such as interferon-α, S100 calcium-binding protein A1 (S100A1) with relatively weak (micromolar) dissociation constant and change conformation of these proteins by affecting their secondary structures [ 10 , 11 ].…”

“…Theoretically, aptamers can be used therapeutically in any disease for which extracellular blocking of protein–protein interactions is required [ 2 , 8 , 9 ]. 2′-5′-Oligoadenylates (2′-5′-As) can bind to some proteins (interferon-α, S100 calcium-binding protein A1) of signaling pathways of innate immunity with relatively weak (micromolar) dissociation constant and change a conformation of these proteins [ 10 , 11 ].…”

Inhibition of hemagglutinin-glycan interaction by complexes of oligoribonucleotides with D-mannitol

“…Отримані результати свідчать про те, що ОРН-D-M можуть розпізнавати ГА вірусу грипу, ймовірно, на або навколо рецепторзв'язуючого місця, який необхідний для проникнення вірусу грипу в клітину-хазяїна [13]. Також результати дослідження вказують на можливе потенційне зв'язування ОРН-D-M з амінокислотами біля гліканзв'язуючого місця ГА [1], змінюючи його конформацію [14], що призводить до ефективного перешкоджання ГА-глікановій взаємодії і значно послаблює здатність вірусу проникати в клітину господаря. Оскільки індукований апоптоз під час інфекції вірусу грипу є основним фактором, що призводить до загибелі клітин та пошкодження тканин [15], ми припустили, що ОРН-D-M можуть пригнічувати зв'язування вірусу грипу з клітинами MDCK.…”

Complexes of Oligoribonucleotides with d-Mannitol Modulate the Innate Immune Response to Influenza A Virus H1N1 (A/FM/1/47) In Vivo

“…Theoretically, aptamers can be used therapeutically in any disease [ 18 , 19 , 20 ]. 2′-5′-Oligoadenylates have antiviral actives and can bind to some proteins (interferon α, S100 calcium-binding protein A1, protein kinases), which changes the conformation of these proteins [ 21 , 22 , 23 ].…”