Secondary structure prediction of the H5 pore of potassium channels.

Abstract

The 'H5' segment located between the putative fifth and sixth transmembrane helices is the most highly conserved region in voltage-gated potassium channels and it is believed to constitute a major part of the ion conduction path (pore). Here we present a two-step procedure, comprising secondary structure prediction and hydrophobic moment profiling, to predict the structure of this important region. Combined results from the application of the procedure to the H5 region of four voltage-gated and five other K+ channel sequences lead to the prediction of a beta-strand-turn-beta-strand structure for H5. The reasons for the application of these soluble protein methods to parts of membrane proteins are: (i) that pore-lining residues are accessible to water and (ii) that a large enough database of high-resolution membrane protein structures does not yet exist. The results are compared with experimental results, in particular spectroscopic studies of two peptides based on the H5 sequence of SHAKER potassium channel. The procedure developed here may be applicable to water-accessible regions of other membrane proteins.