The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Determinant for β-subunit regulation in high-conductance voltage-activated and Ca 2+ -sensitive K + channels: An additional transmembrane region at the N terminus
Open accessAbstract
The pore-forming α subunit of large conductance voltage- and Ca 2+ -sensitive K (MaxiK) channels is regulated by a β subunit that has two membrane-spanning regions separated by an extracellular loop. To investigate the structural determinants in the pore-forming α subunit necessary for β-subunit modulation, we made chimeric constructs between a human MaxiK channel and the Drosophila homologue, which we show is insensitive to β-subunit modulation, and analyzed the topology of the α subunit. A comparison of multiple sequence alignments with hydrophobicity plots revealed that MaxiK channel α subunits have a unique hydrophobic segment (S0) at the N terminus. This segment is in addition to the six putative transmembrane segments (S1–S6) usually found in voltage-dependent ion channels. The transmembrane nature of this unique S0 region was demonstrated by in vitro translation experiments. Moreover, normal functional expression of signal sequence fusions and in vitro N-linked glycosylation experiments indicate that S0 leads to an exoplasmic N terminus. Therefore, we propose a new model where MaxiK channels have a seventh transmembrane segment at the N terminus (S0). Chimeric exchange of 41 N-terminal amino acids, including S0, from the human MaxiK channel to the Drosophila homologue transfers β-subunit regulation to the otherwise unresponsive Drosophila channel. Both the unique S0 region and the exoplasmic N terminus are necessary for this gain of function.
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Cites
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Metadata
- Authors
- Wallner, M., Meera, P., & Toro, L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-12-10
- Volume
- 93
- Issue
- 25
- Pages
- 14922-14927
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1990705961
- Cited by
- 271
- References
- 38
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wallner, M., Meera, P., & Toro, L. (1996). Determinant for β-subunit regulation in high-conductance voltage-activated and Ca 2+ -sensitive K + channels: An additional transmembrane region at the N terminus. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.25.14922
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