Structural Research of Calcium Ion-Selective Channels

The regulation of calcium ion concentrations within cells is tightly controlled by a variety of mechanisms, including the activity of calcium ion-selective channels. These channels are responsible for allowing calcium ions to flow across cellular membranes, and their malfunction has been implicated in a number of diseases, including heart disease, Alzheimer's disease, and cancer.

One of the most well-studied types of calcium ion-selective channels is the voltage-gated calcium (Cav) channel, which is found in a variety of cell types throughout the body. Several high-resolution structures of Cav channel have been obtained using X-ray crystallography and cryo-electron microscopy (cryo-EM) techniques. These structures have revealed the location of important functional domains within the channel, as well as the specific interactions between the channel and various ligands, such as calcium ions and drugs that modulate channel activity.

The Cav1 channels Cav1 channels are hetero-multimeric complexes encompassing various subunits including the pore-forming α1 core subunit and auxiliary subunits α2δ, β, and γ. The α1 subunit folds into four homologous repeats I-IV, which are aligned in a canonical voltage-gated ion channel fold. Each repeat encompasses six transmembrane segments, denoted as S1-S6, which are arranged in two functional entities. The peripheral voltage sensing domain of the Cav1 channels comprises the S1-S4 segments in each repeat. The S5 and S6 segments, in combination with the intervening segments, including the selectivity filters and the supporting helices P1 and P2, derived from the four repeats, ultimately come together to form the central ion-conducting pore domain of these channels.

Figure 1. Molecular basis for rCav1.1 modulation by chemical ligands. (Zhao Y, et al., 2019)

Table 1. Structural Research of Calcium Ion-Selective Channels.

At Creative Biostructure, we are committed to providing high-quality structural analysis services and expertise to help our clients advance their research and achieve their scientific goals. Our team of experienced scientists has extensive expertise in X-ray crystallography, cryo-EM, NMR spectroscopy and other structural biology techniques, and we use first-class equipment and software to obtain high-resolution structures of our client's target proteins.

In general, our structural analysis services include protein expression and purification, structure determination using X-ray crystallography or cryo-EM, and structure validation and refinement. We also offer additional services, such as ligand binding studies and functional assays, to provide a comprehensive understanding of the structure and function of target proteins.

If you are interested in learning more about our structural analysis services for calcium ion-selective channels or other membrane proteins, please don't hesitate to contact us. Our team of experts will be happy to discuss your project and provide a customized solution to meet your needs.

References

1. Zhao Y, et al. Molecular basis for ligand modulation of a mammalian voltage-gated Ca2+ channel. Cell. 2019, 177(6): 1495-1506. e12.
2. Gao Y, et al. Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2. 3. Nature Communications. 2023, 14(1): 516.
3. Schmitz E A, Takahashi H, Karakas E. Structural basis for activation and gating of IP3 receptors. Nature Communications. 2022, 13(1): 1408.