Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1848, Issue 10, Pages 2430-2436Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2015.07.016
Keywords
Sodium pump; Regulation; Glutathionylation; Beta-subunit; Phosphatidylcholine; Plasma membrane
Categories
Funding
- National Health and Medical Research Council (Australia) [633252]
- Australian Research Council [DP-121003548, DP-150101112]
- Lundbeck Foundation [R82-2011-7280] Funding Source: researchfish
Ask authors/readers for more resources
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 beta-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 alpha-beta 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 beta-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. (c) 2015 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available