|Title:||Membrane accessibility of glutathione|
Eljack, Nasma D.
Rasmussen, Helge H.
Clarke, Ronald J.
|Citation:||Garcia, A., Eljack, N. D., Sani, M.-A., Separovic, F., Rasmussen, H. H., Kopec, W., … Clarke, R. J. (2015). Membrane accessibility of glutathione. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1848(10), 2430–2436. https://doi.org/10.1016/j.bbamem.2015.07.016|
|Abstract:||Regulation of the ion pumping activity of the Na+,K+-ATPase is crucial to the survival of animal cells. Recent evidence has suggested that the activity of the enzyme could be controlled by glutathionylation of cysteine residue 45 of the β-subunit. Crystal structures so far available indicate that this cysteine is in a transmembrane domain of the protein. Here we have analysed via fluorescence and NMR spectroscopy as well as molecular dynamics simulations whether glutathione is able to penetrate into the interior of a lipid membrane. No evidence for any penetration of glutathione into the membrane was found. Therefore, the most likely mechanism whereby the cysteine residue could become glutathionylated is via a loosening of the -β subunit association, creating a hydrophilic passageway between them to allow access of glutathione to the cysteine residue. By such a mechanism, glutathionylation of the protein would be expected to anchor the modified cysteine residue in a hydrophilic environment, inhibiting further motion of the β-subunit during the enzyme’s catalytic cycle and suppressing enzymatic activity, as has been experimentally observed. The results obtained, therefore, suggest a possible structural mechanism of how the Na+,K+-ATPase could be regulated by glutathione.|
|Rights and Permissions:||© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license|
|Type of Work:||Article|
|Type of Publication:||Post-print|
|Appears in Collections:||Research Papers and Publications. Science|
|BBABiomembr2015_Garcia.pdf||550.53 kB||Adobe PDF|
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