The voltage-gated potassium channel: Sequence analysis and molecular modelling of the pore domain

Abstract

Molecular modelling studies of the transmembrane domain, and in particular of the pore-forming region, of voltage-gated K+ channels are reviewed. Sequence analysis methods are used to define transmembrane helices and their orientation within the intact channel protein. A detailed comparison is presented of three models (from different research groups) of the (H5)4 domain. These models have all been generated by systematic attempts to fit experimental data which identify pore-lining sidechains. The models are analysed in terms of pore radius profiles and predicted conductances, as well as the extent of their agreement with published mutagenesis data. An extended pore domain model, (S5-H5-S6)4, which includes the S5 and S6 helices packed around a bulged β-barrel of (H5)4, is also described and analysed.

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Correspondence to Mark S.P. Sansom.

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Kerr, I.D., Ranatunga, K.M. & Sansom, M.S. The voltage-gated potassium channel: Sequence analysis and molecular modelling of the pore domain. Perspectives in Drug Discovery and Design 15, 187–214 (1999). https://doi.org/10.1023/A:1017024410293

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  • ion channel
  • membrane protein
  • molecular modelling
  • secondary structure prediction