Thermodynamic Analysis of Electromechanical Coupling

Creative Bioarray focuses on the thermodynamics of the conformational coupling between the voltage sensing domain and the central pore in voltage-gated ion channels, known as electromechanical coupling, to help our clients in-depth study of the biophysical mechanisms of voltage sensing. We combine multidisciplinary approaches such as calorimetry, structural biology, and electrophysiology to provide clients with a wide range of scientific services in related fields.

Introduction

The voltage-gated ion channel superfamily has multiple members that share a common overall architecture, including the voltage-sensing domain, the main element of sensing membrane potential changes composed of S1-S4 segments, and the central pore formed by the combination of four S5-S6 segments. Although these members have a conserved overall structure, the interactions and conformational changes between the voltage sensor and the functional pore domain are quite different.

Current advances in biophysical technology have greatly advanced the structural characterization of channels in the gating process, providing better three-dimensional views of the structure of channels in different conformational states and important information for identifying key residues involved in mediating electromechanical coupling. However, the molecular driving forces that underlie these conformational changes and the biophysical mechanisms of the electromechanical coupling remain unclear. Therefore, there is an urgent need to develop some new experimental and analytical tools to quantify the interactions in electromechanical coupling systems and identify these interactors.

Fig. 1 Forces governing voltage sensor pore coupling. (Chowdhury, 2012)

Our Services

Combined with our high-resolution structural characterization services for voltage-gated ion channels, our researchers have developed a variety of experimental means for quantifying the energetic contributions of various structural elements to electromechanical coupling processes to help our clients analyze the thermodynamic and biophysical mechanisms in the process. We determine the contributions of various structural elements and identify the interaction networks involved in energy transfer by estimating the electromechanical coupling energy. The services we provide include but not limited to:

• Characterization of electromechanical coupling pathways in channels.
  We provide our clients with several quantitative methods to measure coupling energies, including integrated and discretized measures of allosteric coupling.
• Mapping of the electromechanical coupling pathways in channels.
  We provide our clients with several semi-quantitative approaches, such as voltage-clamp fluorometry to map possible pathways of allosteric energy transduction.
• Quantification of coupling interactions and identification of perturbations.
• Temperature dependence analysis of electromechanical coupling.

Applications

• Research on the mechanisms of electromechanical coupling
• Research on dynamic regulation of the electromechanical coupling
• Development of new intervention strategies

Creative Bioarray has established a variety of thermodynamic tools and analysis methods to provide clients with thermodynamic analysis services of electromechanical coupling, providing valuable information for the in-depth understanding of the coupling interaction between the voltage-sensing domain and the gates in the pore domain. If you are interested in our services, please contact us for more details.

Reference

1. Chowdhury, S.; Chanda, B. Thermodynamics of electromechanical coupling in voltage-gated ion channels. Journal of General Physiology, 2012, 140(6): 613-623.