THE PORE-LINING REGION OF SHAKER VOLTAGE-GATED POTASSIUM CHANNELS - COMPARISON OF BETA-BARREL AND ALPHA-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 chann el, the structure of this region remains unknown. We have interpreted the available biochemical data as a set of topological and orientation al restraints and employed these restraints to produce molecular model s of the potassium channel pore region, H5. The H5 sequence has been m odeled either as a tetramer of membrane-spanning beta-hairpins, thus p roducing an eight-stranded beta-barrel, or as a tetramer of incomplete ly membrane-spanning alpha-helical hairpins, thus producing an eight-s taved alpha-helix bundle. In total, restraints-directed modeling has p roduced 40 different configurations of the beta-barrel model, each con figuration comprising an ensemble of 20 structures, and 24 different c onfigurations of the alpha-helix bundle model, each comprising an ense mble of 24 structures. Thus, over 1300 model structures for H5 have be en generated. Configurations have been ranked on the basis of their pr edicted pore properties and on the extent of their agreement with the biochemical data. This ranking is employed to identify particular conf igurations of H5 that may be explored further as models of the pore-li ning region of the voltage-gated potassium channel pore.