An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels
Calmodulin (CaM) binding to the AB module is crucial for multiple mechanisms governing the function of Kv7.2 (also known as KCNQ2) K+ channel subunits, which mediate one of the main components of the non-inactivating K+ M-current, a key controller of neuronal excitability. Structural analysis indica...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/421121 |
| Acceso en línea: | http://hdl.handle.net/10261/421121 https://api.elsevier.com/content/abstract/scopus_id/84939484875 |
| Access Level: | acceso abierto |
| Palabra clave: | Signal transduction Calmodulin KCNQ M-current PIP2 |
| Sumario: | Calmodulin (CaM) binding to the AB module is crucial for multiple mechanisms governing the function of Kv7.2 (also known as KCNQ2) K+ channel subunits, which mediate one of the main components of the non-inactivating K+ M-current, a key controller of neuronal excitability. Structural analysis indicates that the CaM N-lobe engages with helix B, whereas the C-lobe anchors to the IQ site within helix A. Here, we report the identification of a new site between helices A and B that assists in CaM binding whose sequence is reminiscent of the TW helix within the CaM C-lobe anchoring site of SK2 K+ channels (also known as KCNN2). Mutations that disrupt CaM binding within the TW site, helix B or helix A yield functional channels, whereas no function is observed when the TW site and helix A, or the TW site and helix B are mutated simultaneously. Our data indicate that the TW site is dispensable for function, contributes to the stabilization of the CaM–Kv7.2 complex and becomes essential when docking to either helix A or when helix B is perturbed. |
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