Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function
The signaling or non-pumping Na,K-ATPase function was first observed by us in the nociceptive neuron; Na,K-ATPase transduced the signals from the opioid-like receptors to Na<sub>V</sub>1.8 channels. This study elucidates the role of the rhamnosyl residue of ouabain in the activation of t...
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2023-07-01
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| author | Ilya V. Rogachevskii Dmitriy M. Samosvat Valentina A. Penniyaynen Vera B. Plakhova Svetlana A. Podzorova Ke Ma Georgy G. Zegrya Boris V. Krylov |
| author_facet | Ilya V. Rogachevskii Dmitriy M. Samosvat Valentina A. Penniyaynen Vera B. Plakhova Svetlana A. Podzorova Ke Ma Georgy G. Zegrya Boris V. Krylov |
| author_sort | Ilya V. Rogachevskii |
| collection | DOAJ |
| description | The signaling or non-pumping Na,K-ATPase function was first observed by us in the nociceptive neuron; Na,K-ATPase transduced the signals from the opioid-like receptors to Na<sub>V</sub>1.8 channels. This study elucidates the role of the rhamnosyl residue of ouabain in the activation of the Na,K-ATPase signaling function. The effects resulting from activation of Na,K-ATPase signaling by the Ca<sup>2+</sup> chelate complex of ouabain (EO) are not manifested upon removal of the rhamnosyl residue, as demonstrated in viable cells by the highly sensitive patch-clamp and organotypic cell culture methods. Docking calculations show that the rhamnosyl residue is involved in five intermolecular hydrogen bonds with the Na,K-ATPase α1-subunit, which are fundamentally important for activation of the Na,K-ATPase signaling function upon EO binding. The main contribution to the energy of EO binding is provided by its steroid core, which forms a number of hydrogen bonds and hydrophobic interactions with Na,K-ATPase that stabilize the ligand–receptor complex. Another critically important role in EO binding is expected to be played by the chelated Ca<sup>2+</sup> cation, which should switch on strong intermolecular ionic interactions between the EO molecule and two α1-Na,K-ATPase amino acid residues, Glu116 and Glu117. |
| first_indexed | 2024-03-11T00:54:25Z |
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| language | English |
| last_indexed | 2024-03-11T00:54:25Z |
| publishDate | 2023-07-01 |
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| series | Life |
| spelling | doaj.art-0d52d25ceb894e7ea68472b2f77831472023-11-18T20:09:20ZengMDPI AGLife2075-17292023-07-01137150010.3390/life13071500Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling FunctionIlya V. Rogachevskii0Dmitriy M. Samosvat1Valentina A. Penniyaynen2Vera B. Plakhova3Svetlana A. Podzorova4Ke Ma5Georgy G. Zegrya6Boris V. Krylov7Pavlov Institute of Physiology of the Russian Academy of Sciences, 199034 Saint Petersburg, RussiaIoffe Institute of the Russian Academy of Sciences, 194021 Saint Petersburg, RussiaPavlov Institute of Physiology of the Russian Academy of Sciences, 199034 Saint Petersburg, RussiaPavlov Institute of Physiology of the Russian Academy of Sciences, 199034 Saint Petersburg, RussiaPavlov Institute of Physiology of the Russian Academy of Sciences, 199034 Saint Petersburg, RussiaDepartment of Pain Management, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200240, ChinaPavlov Institute of Physiology of the Russian Academy of Sciences, 199034 Saint Petersburg, RussiaPavlov Institute of Physiology of the Russian Academy of Sciences, 199034 Saint Petersburg, RussiaThe signaling or non-pumping Na,K-ATPase function was first observed by us in the nociceptive neuron; Na,K-ATPase transduced the signals from the opioid-like receptors to Na<sub>V</sub>1.8 channels. This study elucidates the role of the rhamnosyl residue of ouabain in the activation of the Na,K-ATPase signaling function. The effects resulting from activation of Na,K-ATPase signaling by the Ca<sup>2+</sup> chelate complex of ouabain (EO) are not manifested upon removal of the rhamnosyl residue, as demonstrated in viable cells by the highly sensitive patch-clamp and organotypic cell culture methods. Docking calculations show that the rhamnosyl residue is involved in five intermolecular hydrogen bonds with the Na,K-ATPase α1-subunit, which are fundamentally important for activation of the Na,K-ATPase signaling function upon EO binding. The main contribution to the energy of EO binding is provided by its steroid core, which forms a number of hydrogen bonds and hydrophobic interactions with Na,K-ATPase that stabilize the ligand–receptor complex. Another critically important role in EO binding is expected to be played by the chelated Ca<sup>2+</sup> cation, which should switch on strong intermolecular ionic interactions between the EO molecule and two α1-Na,K-ATPase amino acid residues, Glu116 and Glu117.https://www.mdpi.com/2075-1729/13/7/1500ouabageninouabainrhamnosyl residueNa,K-ATPaseNa<sub>V</sub>1.8 channelpatch-clamp method |
| spellingShingle | Ilya V. Rogachevskii Dmitriy M. Samosvat Valentina A. Penniyaynen Vera B. Plakhova Svetlana A. Podzorova Ke Ma Georgy G. Zegrya Boris V. Krylov Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function Life ouabagenin ouabain rhamnosyl residue Na,K-ATPase Na<sub>V</sub>1.8 channel patch-clamp method |
| title | Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function |
| title_full | Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function |
| title_fullStr | Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function |
| title_full_unstemmed | Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function |
| title_short | Role of the Rhamnosyl Residue of Ouabain in the Activation of the Na,K-ATPase Signaling Function |
| title_sort | role of the rhamnosyl residue of ouabain in the activation of the na k atpase signaling function |
| topic | ouabagenin ouabain rhamnosyl residue Na,K-ATPase Na<sub>V</sub>1.8 channel patch-clamp method |
| url | https://www.mdpi.com/2075-1729/13/7/1500 |
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