The topogenic function of S4 promotes membrane insertion of the voltage-sensor domain in the KvAP channel
| Autor: | Kei Nanatani, Masao Sakaguchi, Jong-Kook Lee, Eriko Mishima, Naomi Hoshi, Nina Schiller, Yoko Sato, Nobuyuki Uozumi, Gunnar von Heijne |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Biological Biochemistry 03 medical and health sciences Dogs 0302 clinical medicine Protein Domains Animals Molecular Biology Membrane potential Transmembrane channels Voltage-gated ion channel Chemistry Cell Biology Voltage-gated potassium channel Transmembrane protein Potassium channel Protein Transport Transmembrane domain 030104 developmental biology Membrane Potassium Channels Voltage-Gated Biophysics Rabbits 030217 neurology & neurosurgery Plasmids |
| Zdroj: | Biochemical Journal. 473:4361-4372 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Voltage-dependent K+ (KV) channels control K+ permeability in response to shifts in the membrane potential. Voltage sensing in KV channels is mediated by the positively charged transmembrane domain S4. The best-characterized KV channel, KvAP, lacks the distinct hydrophilic region corresponding to the S3–S4 extracellular loop that is found in other K+ channels. In the present study, we evaluated the topogenic properties of the transmembrane regions within the voltage-sensing domain in KvAP. S3 had low membrane insertion activity, whereas S4 possessed a unique type-I signal anchor (SA-I) function, which enabled it to insert into the membrane by itself. S4 was also found to function as a stop-transfer signal for retention in the membrane. The length and structural nature of the extracellular S3–S4 loop affected the membrane insertion of S3 and S4, suggesting that S3 membrane insertion was dependent on S4. Replacement of charged residues within the transmembrane regions with residues of opposite charge revealed that Asp72 in S2 and Glu93 in S3 contributed to membrane insertion of S3 and S4, and increased the stability of S4 in the membrane. These results indicate that the SA-I function of S4, unique among K+ channels studied to date, promotes the insertion of S3 into the membrane, and that the charged residues essential for voltage sensing contribute to the membrane-insertion of the voltage sensor domain in KvAP. |
| Databáze: | OpenAIRE |
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