A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

Research output: Contribution to journalJournal articleResearchpeer-review

  • Nathalie Strutz-Seebohm
  • Ulrike Henrion
  • Schmitt, Nicole
  • Eric Schulze-Bahr
  • Guiscard Seebohm
Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods: Here, we study the impact of these residues on ion selectivity, permeation and inactivation kinetics as well as the modulation by β-subunits using site-specific mutagenesis, electrophysiological analyses and molecular dynamics simulations. Results: We identify this position as key in modulation of slow inactivation by structurally dissimilar β-subunits in different KV channels. Conclusion: We propose a model in which structural changes accompanying activation and β-subunit modulation allosterically constrain the backbone carbonyl oxygen atoms via the side chain of the respective X-residue in the signature sequence to reduce conductance during slow inactivation.
Original languageEnglish
JournalCellular Physiology and Biochemistry
Issue number6
Pages (from-to)968-980
Number of pages13
Publication statusPublished - 26 Jun 2013

ID: 47327687