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

João H. Morals Cabral, Alice Lee, Steven L. Cohen, Brian T. Chait, Min Li, Roderick Mackinnon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalCell
Volume95
Issue number5
StatePublished - Nov 25 1998

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Long QT Syndrome
Mutagenesis
Functional analysis
Potassium Channels
Crystal structure
Scanning
Light
Sensors
Electric potential
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Morals Cabral, J. H., Lee, A., Cohen, S. L., Chait, B. T., Li, M., & Mackinnon, R. (1998). Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain. Cell, 95(5), 649-655.

Crystal structure and functional analysis of the HERG potassium channel N terminus : A eukaryotic PAS domain. / Morals Cabral, João H.; Lee, Alice; Cohen, Steven L.; Chait, Brian T.; Li, Min; Mackinnon, Roderick.

In: Cell, Vol. 95, No. 5, 25.11.1998, p. 649-655.

Research output: Contribution to journalArticle

Morals Cabral, JH, Lee, A, Cohen, SL, Chait, BT, Li, M & Mackinnon, R 1998, 'Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain', Cell, vol. 95, no. 5, pp. 649-655.
Morals Cabral JH, Lee A, Cohen SL, Chait BT, Li M, Mackinnon R. Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain. Cell. 1998 Nov 25;95(5):649-655.
Morals Cabral, João H. ; Lee, Alice ; Cohen, Steven L. ; Chait, Brian T. ; Li, Min ; Mackinnon, Roderick. / Crystal structure and functional analysis of the HERG potassium channel N terminus : A eukaryotic PAS domain. In: Cell. 1998 ; Vol. 95, No. 5. pp. 649-655.
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