Voltage sensor ring in a native structure of a membrane-embedded potassium channel

Liang Shi, Hongjin Zheng, Hui Zheng, Brian A. Borkowski, Dan Shi, Tamir Gonen, Qiu Xing Jiang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Voltage-gated ion channels support electrochemical activity in cells and are largely responsible for information flow throughout the nervous systems. The voltage sensor domains in these channels sense changes in transmembrane potential and control ion flux across membranes. The X-ray structures of a few voltage-gated ion channels in detergents have been determined and have revealed clear structural variations among their respective voltage sensor domains. More recent studies demonstrated that lipids around a voltagegated channel could directly alter its conformational state in membrane. Because of these disparities, the structural basis for voltage sensing in nativemembranes remains elusive. Here, through electroncrystallographic analysis of membrane-embedded proteins, we present the detailed view of a voltage-gated potassium channel in its inactivated state. Contrary to all known structures of voltage-gated ion channels in detergents, our data revealed a unique conformation in which the four voltage sensor domains of a voltage-gated potassium channel from Aeropyrum pernix (KvAP) form a ring structure that completely surrounds the pore domain of the channel. Such a structure is named the voltage sensor ring. Our biochemical and electrophysiological studies support that the voltage sensor ring represents a physiological conformation. These data together suggest that lipids exert strong effects on the channel structure and that these effects may be changed upon membrane disruption. Our results have wide implications for lipid-protein interactions in general and for the mechanism of voltage sensing in particular.

Original languageEnglish (US)
Pages (from-to)3369-3374
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Feb 26 2013


  • Cryo-EM
  • Electron crystallography
  • Membrane protein

ASJC Scopus subject areas

  • General


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