Tethering chemistry and K+ channels
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Animals; Biochemistry; Crystallography, X-Ray; Cysteine; Electrophysiology; Humans; Ion Channel Gating; Ligands; Membrane Potentials; Models, Biological; Models, Chemical; Molecular Conformation; Neurons; Potassium Channels, Voltage-Gated; Protein Conformation
Life Sciences | Medicine and Health Sciences
Voltage-gated K+ channels are dynamic macromolecular machines that open and close in response to changes in membrane potential. These multisubunit membrane-embedded proteins are responsible for governing neuronal excitability, maintaining cardiac rhythmicity, and regulating epithelial electrolyte homeostasis. High resolution crystal structures have provided snapshots of K+ channels caught in different states with incriminating molecular detail. Nonetheless, the connection between these static images and the specific trajectories of K+ channel movements is still being resolved by biochemical experimentation. Electrophysiological recordings in the presence of chemical modifying reagents have been a staple in ion channel structure/function studies during both the pre- and post-crystal structure eras. Small molecule tethering agents (chemoselective electrophiles linked to ligands) have proven to be particularly useful tools for defining the architecture and motions of K+ channels. This Minireview examines the synthesis and utilization of chemical tethering agents to probe and manipulate the assembly, structure, function, and molecular movements of voltage-gated K+ channel protein complexes.
Rights and Permissions
Citation: J Biol Chem. 2008 Sep 12;283(37):25105-9. Epub 2008 Jun 9. Link to article on publisher's site
DOI of Published Version
The Journal of biological chemistry
Morin, Trevor J. and Kobertz, William R., "Tethering chemistry and K+ channels" (2008). GSBS Student Publications. 1517.