Ng, Chai Ann and Phan, Kevin and Hill, Adam P and Vandenberg, Jamie I and Perry, Matthew D (2014) Multiple interactions between cytoplasmic domains regulate slow deactivation of Kv11.1 channels. The Journal of Biological Chemistry, 289 (37). pp.25822-32. ISSN 1083-351X (PMC OA)
Full text not available from this repository.Abstract
The intracellular domains of many ion channels are important for fine-tuning their gating kinetics. In Kv11.1 channels, the slow kinetics of channel deactivation, which are critical for their function in the heart, are largely regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant cycle analysis to probe for functional interactions between the N-Cap/PAS domains and the cNBH domain. We identified a specific and stable charge-charge interaction between Arg(56) of the PAS domain and Asp(803) of the cNBH domain, as well an additional interaction between the cNBH domain and the N-Cap, both of which are critical for maintaining slow deactivation kinetics. Furthermore, we found that positively charged arginine residues within the disordered region of the N-Cap interact with negatively charged residues of the C-linker domain. Although this interaction is likely more transient than the PAS-cNBD interaction, it is strong enough to stabilize the open conformation of the channel and thus slow deactivation. These findings provide novel insights into the slow deactivation mechanism of Kv11.1 channels.
(Heart Foundation of Australia grant NHFA G11S 5829S and NHMRC grants 635520, 459401 and 1019693).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 21 Jan 2016 05:33 |
| Last Modified: | 29 Jun 2016 23:24 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/206 |
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