Three-dimensional structure of human voltage-gated ion channel Kv10.2 studied by electron microscopy of macromolecules and molecular modeling

Three-dimensional structure of the human voltage-gated channel Kv10.2 has been elucidated for the first time using the method of electron microscopy with 2.5 nm resolution. The molecule has a distinct domain structure. For interpretation of the structure, homology modeling was used with the cAMP-dependent channel MlotiK1 (C-subunit) structure used as a template for a membrane part of the channel, homology with the structure of the human potassium channel herg (A subunits) was used for the cytoplasmic subdomains PAS-PAC, and for the cNBD domain homology with the MloK1 channel was used. The homologous transmembrane part corresponds by size to the upper part of the three-dimensional reconstruction. Cytoplasmic domains of the Kv10.2 channel form the structure built according to the ‘hanging gondola’ type that is connected with the transmembrane part of the channel by linkers. The length of linkers suggests the possibility of contacts between the C-terminal cNBD domains and N-terminal PAS-domains.