The pore-lining region of shaker voltage-gated potassium channels: comparison of β-barrel and α-helix bundle models

Although there is a large body of site-directed mutagenesis data that identify the pore-lining sequence of the voltage-gated potassium channel, the structure of this region remains unknown. We have interpreted the available biochemical data as a set of topological and orientational restraints and employed these restraints to produce molecular models of the potassium channel pore region, H5. The H5 sequence has been modeled either as a tetramer of membrane-spanning β-hairpins, thus producing an eight-stranded β-barrel, or as a tetramer of incompletely membrane-spanning α-helical hairpins, thus producing an eight-staved α-helix bundle. In total, restraints-directed modeling has produced 40 different configurations of the β-barrel model, each configuration comprising an ensemble of 20 structures, and 24 different configurations of the α-helix bundle model, each comprising an ensemble of 24 structures. Thus, over 1300 model structures for H5 have been generated. Configurations have been ranked on the basis of their predicted pore properties and on the extent of their agreement with the biochemical data. This ranking is employed to identify particular configurations of H5 that may be explored further as models of the pore-lining region of the voltage-gated potassium channel pore