Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain

Cell. 1998 Nov 25;95(5):649-55. doi: 10.1016/s0092-8674(00)81635-9.


The HERG voltage-dependent K+ channel plays a role in cardiac electrical excitability, and when defective, it underlies one form of the long QT syndrome. We have determined the crystal structure of the HERG K+ channel N-terminal domain and studied its role as a modifier of gating using electrophysiological methods. The domain is similar in structure to a bacterial light sensor photoactive yellow protein and provides the first three-dimensional model of a eukaryotic PAS domain. Scanning mutagenesis of the domain surface has allowed the identification of a hydrophobic "hot spot" forming a putative interface with the body of the K+ channel to which it tightly binds. The presence of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cation Transport Proteins*
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Electrophysiology
  • Ether-A-Go-Go Potassium Channels
  • Long QT Syndrome / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes / chemistry
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • Protein Conformation*
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Xenopus laevis


  • Cation Transport Proteins
  • Ether-A-Go-Go Potassium Channels
  • KCNH6 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated

Associated data

  • PDB/1BYW