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

Molecular modelling studies of the transmembrane domain, and in particular of the pore-forming region, of voltage-gated K+ channels are reviewed. Sequ ence analysis methods are used to define transmembrane helices and their or ientation within the intact channel protein. A detailed comparison is prese nted of three models (from different research groups) of the (H5)(4) domain . These models have all been generated by systematic attempts to fit experi mental 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 por e domain model, (S5-H5-S6)(4), which includes the S5 and S6 helices packed around a bulged beta-barrel of (H5)(4), is also described and analysed.