AI Article Synopsis
- TRPV5 is a calcium channel that plays a key role in calcium reabsorption, and this study explores how two natural modulators, PI(4,5)P and calmodulin (CaM), interact with it.
- The research utilized cryo-electron microscopy to visualize the structure of TRPV5 when bound to PI(4,5)P and CaM, revealing how PI(4,5)P opens the channel and CaM inhibits it.
- Understanding these interactions enhances our knowledge of TRPV5's modulation, which could be beneficial for future drug development.
Article Abstract
TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P and CaM. The PI(4,5)P structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179994 | PMC |
| http://dx.doi.org/10.1038/s41467-018-06753-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Calmodulin regulates TRPV5 intracellular trafficking and plasma membrane abundance.
J Physiol
December 2024
Department of Medical Biosciences, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
As a member of the transient receptor potential (TRP) superfamily of ion channels, TRPV5 is a unique Ca-selective channel important for active reabsorption of Ca in the kidney. TRPV5-mediated Ca entry into the cell is controlled by a negative feedback mechanism, in which calmodulin (CaM) blocks the TRPV5 pore upon Ca binding. Combining microscopy techniques and biochemical assays, the present study uncovered an auxiliary role for CaM in the regulation of human (h)TRPV5 intracellular trafficking.
View Article and Find Full Text PDFextract regulates oxidative stress to maintain calcium homeostasis and improve diabetic osteoporosis.
Food Sci Nutr
October 2024
Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital Southwest Medical University Luzhou Sichuan China.
Article Synopsis
- - Diabetic osteoporosis (DOP) negatively impacts health for patients with diabetes, prompting a study to investigate the protective effects of the aqueous extract of EUL on DOP mice, induced by a specific diet and a drug.
- - The study found that EUL extract improved various health markers in DOP mice, including reducing blood glucose levels, increasing body weight, and enhancing bone density by increasing beneficial factors while decreasing harmful ones.
- - Results indicated that EUL extract positively influenced the expression of calcium transport proteins and stress-related factors in the kidneys and intestines, ultimately leading to improved bone health in the DOP mice.
Renal expression of calcium and phosphorus transporters: contrasting responses to dietary calcium and microbial phytase in broilers and growing pigs.
Br J Nutr
November 2024
Wageningen University & Research, Animal Nutrition Group, Wageningen6700 AH, the Netherlands.
Enhanced dietary Ca intake linearly increases intestinal Ca absorption in pigs, but not in broilers, suggesting potential differences in whole body Ca homeostasis. To determine the role of kidney in Ca homeostasis in these species, we varied in growing pigs in experiment (Exp) 1, the dietary Ca content 2·0 . 9·6 g/kg and phytase 0 .
View Article and Find Full Text PDFImpact of and Its Combination with Isoflavone Products on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in a Post-Menopausal Osteoporotic Rat Model.
Nutrients
August 2024
Department of Human Nutrition and Dietetics, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, 60-624 Poznan, Poland.
Article Synopsis
- Osteoporosis in menopausal women may benefit from dietary alternatives like probiotics and isoflavones due to side effects of current medications.
- In a study with post-menopausal osteoporotic rats, combining probiotics and isoflavone (daidzein and tempeh) showed positive effects on bone metabolism and histopathology, despite reduced calcium transporter expression.
- However, using probiotics alone did not significantly improve bone health, indicating that the combination approach is more effective and suggesting further investigation into these dietary interactions is needed.
Role of Genetic Testing in Kidney Stone Disease: A Narrative Review.
Curr Urol Rep
December 2024
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Purpose Of Review: Kidney stone disease (KSD) is a common and potentially life-threatening condition, and half of patients experience a repeat kidney stone episode within 5-10 years. Despite the ~50% estimate heritability of KSD, international guidelines have not kept up with the pace of discovery of genetic causes of KSD. The European Association of Urology guidelines lists 7 genetic causes of KSD as 'high risk'.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!