Structure prediction for the down state of a potassium channel voltage sensor

Michael Grabe, Helen C. Lai, Monika Jain, Yuh Nung Jan and Lily Yeh Jan ()
Additional contact information
Michael Grabe: Howard Hughes Medical Institute
Helen C. Lai: Howard Hughes Medical Institute
Monika Jain: Howard Hughes Medical Institute
Yuh Nung Jan: Howard Hughes Medical Institute
Lily Yeh Jan: Howard Hughes Medical Institute

Nature, 2007, vol. 445, issue 7127, 550-553

Abstract: Abstract Voltage-gated potassium (Kv) channels, essential for regulating potassium uptake and cell volume in plants and electrical excitability in animals, switch between conducting and non-conducting states as a result of conformational changes in the four voltage-sensing domains (VSDs) that surround the channel pore1. This process, known as gating, is initiated by a cluster of positively charged residues on the fourth transmembrane segment (S4) of each VSD, which drives the VSD into a ‘down state’ at negative voltages and an ‘up state’ at more positive voltages2. The crystal structure of Kv1.2 probably corresponds to the up state3, but the local environment of S4 in the down state and its motion in voltage gating remains unresolved4,5,6. Here we employed several conditional lethal/second-site suppressor yeast screens to determine the transmembrane packing of the VSD in the down state. This screen relies on the ability of KAT1, a eukaryotic Kv channel, to conduct potassium when its VSDs are in the down state, thereby rescuing potassium-transport-deficient yeast7. Starting with KAT1 channels bearing conditional lethal mutations, we identified second-site suppressor mutations throughout the VSD that recover yeast growth. We then constructed a down state model of the channel using six pairs of interacting residues as structural constraints and verified this model by engineering suppressor mutations on the basis of spatial considerations. A comparison of this down state model with the up state Kv1.2 structure suggests that the VSDs undergo large rearrangements during gating, whereas the S4 segment remains positioned between the central pore and the remainder of the VSD in both states.

Date: 2007
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature05494 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:445:y:2007:i:7127:d:10.1038_nature05494

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05494

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().