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Functional analysis of an archaebacterial voltage-dependent K+ channel

Abstract

All living organisms use ion channels to regulate the transport of ions across cellular membranes1. Certain ion channels are classed as voltage-dependent because they have a voltage-sensing structure that induces their pores to open in response to changes in the cell membrane voltage. Until recently, the voltage-dependent K+, Ca2+ and Na+ channels were regarded as a unique development of eukaryotic cells, adapted to accomplish specialized electrical signalling, as exemplified in neurons. Here we present the functional characterization of a voltage-dependent K+ (KV) channel from a hyperthermophilic archaebacterium from an oceanic thermal vent. This channel possesses all the functional attributes of classical neuronal KV channels. The conservation of function reflects structural conservation in the voltage sensor as revealed by specific, high-affinity interactions with tarantula venom toxins, which evolved to inhibit eukaryotic KV channels.

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Figure 1: Architecture of a voltage-dependent K+ channel.
Figure 2: Properties of the ion pathway.
Figure 3: Voltage-dependent gating properties.
Figure 4: Inhibition by G. spatulata toxins.

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Acknowledgements

We thank M. Trester-Zedlitz for assistance with mass spectrometry and W. Chin for assistance in manuscript preparation. Protein sequence was done at the Rockefeller University Protein/DNA Technology Center (supported by NIH shared instrumentation grants, the US Army and Navy). This research was supported by an NIH grant. V.R. is supported by a NSF graduate student research fellowship and R.M. is an Investigator in the Howard Hughes Medical Institute.

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Correspondence to Roderick MacKinnon.

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Ruta, V., Jiang, Y., Lee, A. et al. Functional analysis of an archaebacterial voltage-dependent K+ channel. Nature 422, 180–185 (2003). https://doi.org/10.1038/nature01473

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