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    The T1-tetramerization domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac Sodium Channel

    D’Avanzo, N. and Miles, Andrew and Powl, Andrew and Nichols, C.G. and Wallace, Bonnie A. and O'Reilly, Andrias (2021) The T1-tetramerization domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac Sodium Channel. FEBS Letters , ISSN 1873-3468. (In Press)

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    Abstract

    Cytoplasmic domains frequently promote functional assembly of multimeric ion channels. To investigate structural determinants of this process, we generated the ‘T1-chimera’ construct of the NaChBac sodium channel by truncating the C-terminal domain and splicing the T1-tetramerisation domain of the Kv1.2 channel to the N-terminus. Purified T1-chimera channels were tetrameric, conducted Na+ when reconstituted into proteliposomes and were blocked by the drug mibefradil. Both the T1-chimera and full-length NaChBac had comparable expression in the membrane whereas a NaChBac mutant lacking a cytoplasmic domain had greatly-reduced membranal expression. Our findings support a model whereby bringing the transmembrane regions into close proximity enables their tetramerization. This phenomemon is found with other channels and thus our findings substantiate this as a common assembly mechanism. Nazzareno ‡, Andrew J. Miles2 ‡, Andrew M. Powl2, Colin G. Nichols3, B.A. Wallace2, Andrias O. O’Reilly4 *

    Metadata

    Item Type: Article
    Additional Information: This is the peer reviewed version of the article, which has been published in final form at the link above. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    Keyword(s) / Subject(s): channel assembly, voltage-gated channel, tetramerization, chimera, membrane expression
    School: School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 11 Jan 2022 14:17
    Last Modified: 04 Jul 2022 12:46
    URI: https://eprints.bbk.ac.uk/id/eprint/47007

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