The TRPV5/6 calcium channels contain multiple calmodulin binding sites with differential binding properties
Nadezda V Kovalevskaya1, Fedir M Bokhovchuk, Geerten W Vuister
1Department of Protein Biophysics, IMM, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands. n.kovalevskaya@science.ru.nl
Journal of Structural and Functional Genomics
|February 23, 2012
Summary
Calmodulin binding to epithelial calcium channels TRPV5/6 differs between subtypes. Researchers identified five calmodulin binding sites, suggesting diverse regulatory mechanisms for calcium reabsorption.
Area of Science:
- Molecular biology
- Cell physiology
- Ion channel function
Background:
- Epithelial calcium channels, transient receptor potential vanilloid 5/6 (TRPV5/6), tightly regulate calcium reabsorption.
- Calmodulin (CaM) is known to mediate calcium-dependent inactivation of TRPV5/6 channels via binding to the C-terminal region.
Purpose of the Study:
- To investigate the detailed binding interactions between calmodulin and TRPV5/6 channels.
- To identify and characterize additional calmodulin binding sites on TRPV5/6.
Main Methods:
- In vitro characterization of calmodulin binding fragments.
- Analysis of binding modes, stoichiometries, and affinities.
Main Results:
- Significant differences in calmodulin binding were observed between TRPV5 and TRPV6 channels.
- Four novel calmodulin binding fragments of TRPV5/6 were identified and characterized.
- The five identified calmodulin binding sites exhibit diverse binding characteristics.
Conclusions:
- Calmodulin interaction with TRPV5/6 channels is complex and subtype-specific.
- The identified binding sites and their diverse properties suggest intricate regulatory mechanisms for calcium homeostasis.
- These findings provide a deeper understanding of TRPV5/6 channel regulation by calcium and calmodulin.
Related Concept Videos
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
01:25Structure of Cadherins
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
01:12Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
01:12Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...