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

Autor: Nazzareno D’Avanzo, Andrew J. Miles, Andrew M. Powl, Colin G. Nichols, B.A. Wallace, Andrias O. O’Reilly
Jazyk: angličtina
Rok vydání: 2022
Předmět:
ISSN: 1873-3468
0014-5793
Popis: 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.\ud \ud Nazzareno ‡, Andrew J. Miles2 ‡, Andrew M. Powl2, Colin G. Nichols3, B.A. Wallace2, Andrias O. O’Reilly4 *
Databáze: OpenAIRE
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