Characterization of Zinc-Activated Channels

Creative Bioarray is committed to developing available pharmacological tools for zinc-activated channels (ZACs) to provide clients with high-quality ZAC characterization services, especially functional pharmacology. Our unmatched study design and execution as well as data analysis capabilities ensure that we can finally submit scientific and reasonable data for our clients.

Introduction

Zinc-activated channel (ZAC) belongs to the superfamily of ligand-gated ion channels and constitutes the fifth branch of the phylogenetic tree over mammalian Cys-loop receptors (CLRs). As its name states, ZAC can be activated by high concentrations of zinc. This channel exhibits low amino acid sequence homology with other CLR subunits and has very different endogenous agonist and signaling properties. Structurally, ZAC, like other ligand-gated ion channels, has four transmembrane domains and extracellular N- and C-termini.

In contrast to the detailed understanding of the in vivo function of the classical CLR gained through decades of research, little is currently known about the physiological roles controlled by ZAC. Although the human ZACN gene is conserved in most other mammalian species, the orthologous genes are not expressed in rodents, which limits the study of the physiological functions of the receptor. There is an urgent need to develop effective and selective pharmacological tools, which will facilitate the study of the in vivo functions governed by ZAC and the therapeutic potential in the receptor.

Fig. 1 Candidate Zn²⁺-binding residues in the extracellular domain of ZAC. (Madjroh, 2021)

Our Services

We have established methods for functional pharmacological characterization of heterologously expressed ZACs to provide our clients with professional ZAC characterization services. We express ZAC in the Xenopus oocyte expression system and help clients analyze ZAC signaling through techniques such as two-electrode voltage clamp (TEVC) electrophysiology and site-directed mutagenesis. Our services include but not limited to:

• Delineation of the agonist binding sites.
• Screening for novel ZAC antagonists.
• Analysis of selectivity profile and action mode of ZAC antagonists.
• Functional characterization of chimeric receptors fusing extracellular domain (ECD) and transmembrane/intracellular domain (TMD-ICD) from ZAC and classical CLRs.
• Investigation of the Zn²⁺ binding site(s) in ZAC.
• Analysis of the functional importance of the Leu9' residue in ZAC.

Applications

• Study on the molecular basis for signal transduction through the ZAC
• Study on the mechanism of agonist-induced ZAC activation
• Study on the mechanism of ZAC gating

Advantages

• State-of-the-art equipment and capabilities
• Unparalleled expertise in ion channels
• Expert consultation
• Innovative, time-efficient, and cost-effective services

Creative Bioarray has extensive experience and expertise in ion channel analysis, including functional pharmacological characterization of ZACs. Our dedicated research team will work with you to develop the best experimental protocol to expand your understanding of this enigmatic member of the CLR superfamily. If you are interested in our services, please contact us for more details.

Reference

1. Madjroh, N.; et al. Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC). Biochemical Pharmacology, 2021, 193: 114781.