Crystal structure of an inactivated mutant mammalian voltage-gated K + channel

Nat Struct Mol Biol. 2017 Oct;24(10):857-865. doi: 10.1038/nsmb.3457. Epub 2017 Aug 28.


C-type inactivation underlies important roles played by voltage-gated K+ (Kv) channels. Functional studies have provided strong evidence that a common underlying cause of this type of inactivation is an alteration near the extracellular end of the channel's ion-selectivity filter. Unlike N-type inactivation, which is known to reflect occlusion of the channel's intracellular end, the structural mechanism of C-type inactivation remains controversial and may have many detailed variations. Here we report that in voltage-gated Shaker K+ channels lacking N-type inactivation, a mutation enhancing inactivation disrupts the outermost K+ site in the selectivity filter. Furthermore, in a crystal structure of the Kv1.2-2.1 chimeric channel bearing the same mutation, the outermost K+ site, which is formed by eight carbonyl-oxygen atoms, appears to be slightly too small to readily accommodate a K+ ion and in fact exhibits little ion density; this structural finding is consistent with the functional hallmark of C-type inactivation.

MeSH terms

  • Crystallography, X-Ray
  • Models, Molecular
  • Mutant Proteins / chemistry*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Protein Conformation
  • Shaker Superfamily of Potassium Channels / chemistry*
  • Shaker Superfamily of Potassium Channels / genetics
  • Shaker Superfamily of Potassium Channels / metabolism*


  • Mutant Proteins
  • Shaker Superfamily of Potassium Channels