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Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward
- Source :
- Journal of molecular biology
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Inter- and intra-molecular allosteric interactions underpin regulation of activity in a variety of biological macromolecules. In the voltage-gated ion channel superfamily, the conformational state of the voltage-sensing domain regulates the activity of the pore domain via such long-range allosteric interactions. Although the overall structure of these channels is conserved, allosteric interactions between voltage-sensor and pore varies quite dramatically between the members of this superfamily. Despite the progress in identifying key residues and structural interfaces involved in mediating electromechanical coupling, our understanding of the biophysical mechanisms remains limited. Emerging new structures of voltage-gated ion channels in various conformational states will provide a better three-dimensional view of the process but to conclusively establish a mechanism, we will also need to quantitate the energetic contribution of various structural elements to this process. Using rigorous unbiased metrics, we want to compare the efficiency of electromechanical coupling between various sub-families in order to gain a comprehensive understanding. Furthermore, quantitative understanding of the process will enable us to correctly parameterize computational approaches which will ultimately enable us to predict allosteric activation mechanisms from structures. In this review, we will outline the challenges and limitations of various experimental approaches to measure electromechanical coupling and highlight the best practices in the field.
- Subjects :
- Computer science
Process (engineering)
voltage-sensing
Allosteric regulation
Ion Channels
Article
Domain (software engineering)
03 medical and health sciences
GIA
0302 clinical medicine
Allosteric Regulation
Structural Biology
Electromechanical coupling
Humans
linkage analysis
Molecular Biology
Ion channel
030304 developmental biology
0303 health sciences
allostery
Voltage-gated ion channel
Mechanism (biology)
Order (biology)
kinetic analysis
Biological system
Ion Channel Gating
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 00222836
- Volume :
- 433
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Biology
- Accession number :
- edsair.doi.dedup.....b70b20e2ad75e3c863ce298e72546276