AI Article Synopsis
- Proteins with the TLDc domain play a significant role in protecting against oxidative stress and are linked to neurological health issues.
- Recent research shows that the yeast TLDc protein, Oxr1p, can inhibit the V-ATPase by causing it to disassemble.
- In this study, five human TLDc proteins were tested, revealing that some inhibit V-ATPase function while one, mEAK7, activates it, providing new insights into their roles in humans.
Article Abstract
Proteins that contain a highly conserved TLDc domain (Tre2/Bub2/Cdc16 LysM domain catalytic) offer protection against oxidative stress and are widely implicated in neurological health and disease. How this family of proteins exerts their function, however, is poorly understood. We have recently found that the yeast TLDc protein, Oxr1p, inhibits the proton pumping vacuolar ATPase (V-ATPase) by inducing disassembly of the pump. While loss of TLDc protein function in mammals shares disease phenotypes with V-ATPase defects, whether TLDc proteins impact human V-ATPase activity directly is unclear. Here we examine the effects of five human TLDc proteins, TLDC2, NCOA7, OXR1, TBC1D24, and mEAK7 on the activity of the human V-ATPase. We find that while TLDC2, TBC1D24, and the TLDc domains of OXR1 and NCOA7 inhibit V-ATPase by inducing enzyme disassembly, mEAK7 activates the pump. The data thus shed new light both on mammalian TLDc protein function and V-ATPase regulation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246223 | PMC |
| http://dx.doi.org/10.1016/j.str.2024.03.009 | DOI Listing |
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