A new "hydrophobic template" method detects segments forming transmembrane α-helical bundles in ion channels

We present a "hydrophobic template" method enabling recognition of alpha-helix bundles in membrane channels from sequence analysis. Inspection of hydrophobic properties of pore-forming helices in proteins with known structure (A-B(5) toxins) permits delineation of a common polarity motif: two hydrophobic surface stretches separated by polar areas. The bundles are stabilized by nonpolar interhelical contacts. A number of transmembrane segments were checked for presence of this motif, and it was detected for pore-forming helices of several ion transporters (segments M2 of acetylcholine and GABAA receptors, alpha 5 peptide of delta-endotoxin), which reveal five alpha-helix bundle architecture. Applications of the method to modeling of membrane channels are discussed.