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Three-dimensional structure of truncated human Kv10.2 ion channel studied by cryoelectron microscopy and molecular modelingтезисы доклада
- Авторы: Glukhov G., Novoseletsky V., Volyntseva A., Shaitan K., Sokolova O.
- Сборник: The FEBS Journal Special Issue for the 41st FEBS Congress
- Том: 283
- Тезисы
- Год издания: 2016
- Место издания: The FEBS Journal KUŞADASI, TURKEY
- Первая страница: 274
- Последняя страница: 274
- DOI: 10.1111/febs.13808
- Аннотация: Voltage-gated potassium channel Kv10.2 belongs to the ether-ago- go family. It has been proved that its mutants are involved in development of neurological diseases and some types of tumor. Directed drug design needs knowledge of details of the threedimensional channel structure. The members of the 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, 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 an improved 3D structure of the truncated human Kv10.2 channel, obtained by single particle EM. This channel lacks its cytoplasmic PAS domain but it still forms tetrameric particles. Earlier we showed 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 cNBD domains. Deletion of the PAS domain leads to the conformational change in the cytoplasmic part of the channel. For interpretation of the 3D structures we used homology modeling and molecular dynamics simulation. There are several templates available to the moment including eag domain-CNBHD complex of the mouse EAG1 channel, full-length Shaker potassium channel Kv1.2, C-linker/CNBHD of zELK channels and others. But there are still no templates for many fragments that led to necessity of partial de novo modeling. Analysis of molecular trajectory allowed estimating dynamical characteristics of channel, supposing interdomain interactions. Results of the conducted investigation have a great interest at both the academic and the industrial levels. This study was supported by Ministry of Education and Science of the Russian Federation grant No. 14.616.21.0044 from 09.10.2015, project ID RFMEFI61615X0044.
- Добавил в систему: Глухов Григорий Сергеевич