D'Avanzo, N, Miles, AJ, Powl, AM, Nichols, CG, Wallace, BA and O'Reilly, AO (2022) The T1-tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel. FEBS Letters. ISSN 0014-5793

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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 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.

Item Type:	Article
Uncontrolled Keywords:	0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 0603 Evolutionary Biology
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Divisions:	Biological & Environmental Sciences (from Sep 19)
Publisher:	Wiley
Related URLs:	Author
Date Deposited:	08 Feb 2022 10:13
Last Modified:	08 Feb 2022 10:15
DOI or ID number:	10.1002/1873-3468.14279
URI:	https://researchonline.ljmu.ac.uk/id/eprint/16249

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