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Three-dimensional structure of Kv ion channel suggests mechanism for its activationтезисы доклада
- Автор: Соколова О.С.
- Сборник: труды 13th annual congress of international drug discovery science and technology-2015
- Тезисы
- Год издания: 2015
- Место издания: Пекин, Китай
- Первая страница: 244
- Аннотация: Voltage-gated potassium Kv channels are widely distributed in the central nervous system, as well as in endocrine cells, heart, lungs and other tissues. The members of the Kv 2 and Kv10-12 subfamilies are characterized by extremely long N- and C-terminal intracellular tails, which possess a number of structural domains. The N-terminal PAS domain in Kv10 plays an important role in activation (Wray, 2004), and is thought to alter the rate of deactivation, possibly by binding at or near the S4-S5 linker at the inner mouth of the pore. Here we present two 3D structures of the full-length and truncated human Kv10.2 channel, obtained by single particle EM. For interpretation of the 3D structures we used homology modeling. We demonstrate that the full length Kv10.2 channel is build according to the ‘hanging gondola’ type, and its cytoplasmic and transmembrane parts are connected by linkers. The cytoplasmic part includes the interconnecting PAS and сNBD domains. Unlike in the related HCN and MlotiK1 channels, in the full-length Kv10.2 channel the C-terminal cNBD domains do not form tetramer. Deletion of the PAS domain leads to the conformational change in the cytoplasmic part of the channel, resulting in formation the tetramer of the cNBD domains. Thus we have for the first time demonstrated the physical contacts between the C-terminal cNBD domains and N-terminal PAS domains in the full-length Kv10 channel. These contacts are mediated by S4-S5 linkers, and may be important for regulation of the channel activation.
- Добавил в систему: Соколова Ольга Сергеевна