title: A common structural component for β-subunit mediated modulation of slow inactivation in different KV channels.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strutz-Seebohm
authors.forename: Ulrike
authors.initials: U
authors.lastname: Henrion
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitt
authors.forename: Eric
authors.initials: E
authors.lastname: Schulze-Bahr
authors.forename: Guiscard
authors.initials: G
authors.lastname: Seebohm
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D051672:Shal Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism
chemical_list: D051657:KCNQ1 Potassium Channel; D051666:Kv1.5 Potassium Channel; D021122:Protein Subunits; D051672:Shal Potassium Channels; D011188:Potassium