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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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The T1-tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
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 |
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| 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: | |
| 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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