The T1-tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel.

Autor: D'Avanzo N; Department of Pharmacology and Physiology, Université de Montréal, Canada., Miles AJ; Institute of Structural and Molecular Biology, Birkbeck, University of London, UK., Powl AM; Institute of Structural and Molecular Biology, Birkbeck, University of London, UK., Nichols CG; Department of Cell Biology and Physiology, Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, USA., Wallace BA; Institute of Structural and Molecular Biology, Birkbeck, University of London, UK., O'Reilly AO; School of Biological & Environmental Sciences, Liverpool John Moores University, UK.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2022 Mar; Vol. 596 (6), pp. 772-783. Date of Electronic Publication: 2022 Jan 19.
DOI: 10.1002/1873-3468.14279
Abstrakt: 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 its 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 proteoliposomes, and were functionally blocked by the drug mibefradil. Both the T1-chimera and full-length NaChBac had comparable expression levels in the membrane, whereas a NaChBac mutant lacking a cytoplasmic domain had greatly reduced membrane expression. Our findings support a model whereby bringing the transmembrane regions into close proximity enables their tetramerisation. This phenomenon is found with other channels, and thus, our findings substantiate this as a common assembly mechanism.
(© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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