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Voltage dependent activation of potassium channels is coupled to T1 domain structure

Nature Structural Biology volume 7, pages 403–407 (2000)Cite this article

Abstract

The T1 domain, a highly conserved cytoplasmic portion at the N-terminus of the voltage-dependent K+ channel (Kv) α-subunit, is responsible for driving and regulating the tetramerization of the α-subunits. Here we report the identification of a set of mutations in the T1 domain that alter the gating properties of the Kv channel. Two mutants produce a leftward shift in the activation curve and slow the channel closing rate while a third mutation produces a rightward shift in the activation curve and speeds the channel closing rate. We have determined the crystal structures of T1 domains containing these mutations. Both of the leftward shifting mutants produce similar conformational changes in the putative membrane facing surface of the T1 domain. These results suggest that the structure of the T1 domain in this region is tightly coupled to the channel's gating states.

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Figure 1: Location of T1 domain point mutations.
Figure 2: T1 mutations alter channel gating.
Figure 3: Analysis of T1 domain tetramer stability.
Figure 4: T1 domain mutations cause specific structural changes in the T1 domain.

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Acknowledgements

P.J.P. acknowledges the support of the NIH and the American Heart Association. M.H.N. acknowledges the fellowship from the American Heart Association. We thank T. Earnest at ALS for data collection. ALS is supported by the Department of Energy. S.C. acknowledges the support from the NIH and the Klingenstein Fellowship award in Neuroscience.

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Authors and Affiliations

  1. Division of Neuroscience, S613, Baylor College of Medicine, 1 Baylor Plaza, Houston, 77030, Texas, USA

    Susan J. Cushman, David DeRubeis & Paul J. Pfaffinger

  2. Structural Biology Lab, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, 92037, California, USA

    Max H. Nanao, Alex W. Jahng & Senyon Choe

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  1. Susan J. Cushman
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  6. Paul J. Pfaffinger
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Correspondence to Paul J. Pfaffinger.

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Cushman, S., Nanao, M., Jahng, A. et al. Voltage dependent activation of potassium channels is coupled to T1 domain structure. Nat Struct Mol Biol 7, 403–407 (2000). https://doi.org/10.1038/75185

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