Structural Characterization of Voltage-Gated Potassium Channels

Creative Bioarray is committed to providing clients with structural characterization services of voltage-gated potassium (K_v) channels using a variety of techniques such as electrophysiology and crystallography. The detailed structural information we provide will help our clients understand how the voltage-sensing domain moves in response to changes in membrane potential and couples this to conformational changes at the pore, accelerating the deciphering of the complex gating mechanisms in K_v channels.

Background

K_v channels play an essential role in the generation and propagation of action potentials. Most K_v channels open when the membrane is depolarized and close when the membrane is hyperpolarized. The K_v channel is a homotetramer composed of 4 functional α subunits, each α subunit contains 6 transmembrane domains S1-S6, which form voltage sensor domain (VSD) (S1-S4) and a pore-forming domain composed of S5 and S6, respectively.

According to the amino acid sequence of the entire hydrophobic core of the protein, K_v channels can be divided into 12 K_v channel subfamilies (K_v1.x~K_v12.x). Studying the structure and function of these complexes has important implications for elucidating their mechanisms of action in controlling neuronal excitability. Recently, advances in electrophysiology, spectroscopy, and crystallography have promoted the extensive structural and functional characterization of K_v channels, providing detailed information for the study of how VSD reports changes in membrane electric fields and couple this with conformational changes in activation gates, as well as how to achieve selectivity in K⁺ channels.

Fig. 1 Structural details of KcsA. (Kim, 2016)

Our Services

Our researchers are committed to providing clients with information on the structure of K⁺ channels in coarse and fine detail through a variety of advanced structural characterization techniques. We have helped clients determine the structures of several bacterial K⁺ channels and isolated eukaryotic K_v channel domains at atomic resolution. However, given that the organization of multiple domains of the intact K_v channel is important, we have also expanded our service to help clients gain new insights into the overall organization of K⁺ channels and their auxiliary subunits. The services we provide include but not limited to:

• Detailed characterization of K⁺ channel pores, such as MthK and KcsA.
• Analysis of conformational changes in pores during activation.
• Structural characterization of VSDs in active and resting states.
• Analysis of conformational changes during N-type inactivation and C-type inactivation.
• Electron microscopic structure analysis of individual K_v channels, such as Eag1 (K_v1), hERG1 (K_v11.1), and KCNQ1 (K_v7.1).
• Structural characterization and interaction analysis of complexes of K_v channels and their auxiliary subunits.

Applications

The structural characterization services we provide are expected to accelerate the research of K_v channels in many aspects.

• Study on K⁺ channel selectivity
• Study on the coupling between the voltage sensor and the channel gate
• Study on the allosteric coupling of N- and C-type mechanisms

Creative Bioarray focuses on developing a series of structural characterization services for voltage-gated ion channels to meet clients' extensive scientific needs in ion channel research. We are dedicated to the structural biology of K_v channels to help you elucidate the structural basis and voltage-gating mechanism of potassium ion selectivity. If you are interested in our services, please contact us for more details.

Reference

1. Kim, D. M.; Nimigean, C. M. Voltage-gated potassium channels: a structural examination of selectivity and gating. Cold Spring Harbor perspectives in biology, 2016, 8(5): a029231.