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Arranging the elements of the potassium channel: the T1 domain occludes the cytoplasmic face of the channel

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Abstract

The voltage-gated potassium channel is currently one of the few membrane proteins where functional roles have been mapped onto specific segments of sequence. Although high-resolution structures of the transmembrane portions of three bacterial potassium channels, the tetramerization domain and the cytoplasmic “ball” are available, their relative spatial arrangement in mammalian channels remains a matter of ongoing debate. Cryo-electron microscopic images of the six transmembrane voltage-gated Kv channel have been reconstructed at up to 18 Å resolution, revealing that the T1 domain tetramerizes and is suspended below the transmembrane segments. However, the resolution of these images is insufficient to reveal the location of the third piece of the puzzle, the inactivating ball domain. We have used the aberrant interactions observed in a series of chimæric channels to establish that an assembled T1 domain restricts access to the cytoplasmic face of the channel, suggesting that the N-terminal “ball and chain” may be confined in the space between the T1 domain and the transmembrane portion of the channel.

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Acknowledgements

A.V. acknowledges support from the Kanwal Rekhi Scholarship of the TIFR Endowment Fund. The authors thank Ms. Kavitha S. for her help with experiments. This work was supported by internal funds from NCBS.

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Author notes

  1. Anurag Varshney

    Present address: Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA

  2. Baron Chanda

    Present address: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Authors and Affiliations

  1. National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, 560 065, Bangalore , India

    Anurag Varshney, Baron Chanda & M. K. Mathew

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  1. Anurag Varshney
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  2. Baron Chanda
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  3. M. K. Mathew
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Correspondence to M. K. Mathew.

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Varshney, A., Chanda, B. & Mathew, M.K. Arranging the elements of the potassium channel: the T1 domain occludes the cytoplasmic face of the channel. Eur Biophys J 33, 370–376 (2004). https://doi.org/10.1007/s00249-003-0372-1

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  • DOI: https://doi.org/10.1007/s00249-003-0372-1

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