Structural Characterization of Voltage-Gated Calcium Channels

Voltage gated calcium channels (VGCC) exist widely in mammals and are closely related to a series of important physiological processes. Creative Bioarray is committed to providing clients with structural characterization services of VGCC through a variety of high-resolution techniques, providing a theoretical basis for exploring the channel properties between different VGCC subfamilies.

Background

Voltage gated calcium channels (VGCC), also known as voltage dependent calcium channels (VDCCs), are a group of large transmembrane multi protein complexes found in the membranes of excitable cells (such as muscles, glial cells, neurons, etc.). VGCC can control cellular calcium entry in response to membrane depolarization and participate in a variety of important physiological processes, such as neurotransmitter and hormone release, cardiac action potential transmission, muscle contraction and calcium dependent gene transcription.

VGCC are composed of several different subunits: α1, α2δ, β1-4 and γ. These proteins work together through complex mechanisms to complete the physiological functions required by the body. In recent years, with the continuous development of molecular biological technology and biophysical technology, such as freeze electron microscopy, researchers have made great progress in parsing the structure of mammalian VGCC. The high-resolution structural study of VGCC components from different isoforms and VGCC regulators provides valuable information for revealing the exceptionally rich feedback modulation infrastructure that controls the role of VGCC.

Fig. 1 Schematic cartoon of a voltage-gated calcium channel. (Petegem, 2006)

Our Services

Our research team has developed a variety of techniques such as cryo-electron microscopy, single-particle cryo-electron microscopy, nuclear magnetic resonance (NMR) and spectroscopy to provide customers with high-quality VGCC structure determination services. Our services include but not limited to:

• High-resolution structural analysis of α1 and β subunits.
• Crystallographic analysis of the functional core of a β-subunit and in complex with a α1-interacting domain (AID) peptide.
• High-resolution structural analysis of different VGCC subtypes such as CaV1.1, CaV3.1.
• Analysis of interaction of VGCC with Ca²⁺/Calmodulin (CaM) and structural analysis of Ca²⁺/CaM-IQ domain complexes.
• Structural analysis of channel modulators that have dramatic effects on VGCC function, such as CaBP1 and Kir/GEM GTPases.
• High-resolution structural analysis of VGCC complex in unbound substrate state and bound small molecule drug state.

Applications

Our precise structural analysis combined with biochemical and functional research can promote the research of VGCC in many aspects.

• Study on interdomain interactions and structural transitions
• Study on calcium channel physiology
• Study on the mechanism of VGCC closed-state inactivation and drug regulation

With an advanced technology platform and a professional research team, Creative Bioarray has the strength to help clients achieve high-resolution VGCC structural analysis, which helps to clarify the action mode and structural basis of different VGCC in mammalian cells, so as to provide certain theoretical and guiding significance for the development of targeted drugs against VGCC dysfunction or disorder. If you are interested in our services, please contact us for more details.

Reference

1. Petegem, F. V.; Minor, D. L. The structural biology of voltage-gated calcium channel function and regulation. Biochemical Society Transactions, 2006, 34(Pt 5):887.