Spatial Localization of the K+ Channel Selectivity Filter by Mutant Cycle–Based Structure Analysis

  title={Spatial Localization of the K+ Channel Selectivity Filter by Mutant Cycle–Based Structure Analysis},
  author={Rama Ranganathan and John H. Lewis and Roderick MacKinnon},
The structurally well-characterized scorpion toxin Agitoxin2 inhibits ion permeation through Shaker K+ channels by binding to the external pore entryway. Scanning mutagenesis identified a set of inhibitor residues critical for making energetic contacts with the channel. Using thermodynamic mutant cycle analysis, we have mapped channel residues relative to the known inhibitor structure. This study constrains the position of multiple channel residues within the pore-forming loops; in one stretch… CONTINUE READING
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