Peptide ion channels

One issue that complicates efforts to develop a model for the mechanism by which peptide ion channels work is the width of the bilayer that must be spanned by the transmembrane helix. Vodyanoy and Hall (251) measured the dielectric thickness of monoglyceride bilayers and found it to vary from 3.1 to 2.0 nm as the fatty acid chain length went from C22 to C14. The crystal structure (252) of the photosynthetic reaction center indicates a 3.0-3.1-nm hydrophobic zone perpendicular to the membrane that is smaller than might be expected for C18 lipids but is in accord with estimates of dielectric thickness as well as recent physical studies (253). With the assumption that a transmembrane segment must span this thickness to give a stable pore structure, a rise per residue of 1.5 A can be estimated for an a-helix, and 20 amino acid residues would be required. Peptides shorter than 20 residues, such as mastoparan and emerimicin, are capable of ion channel formation,... 

Chart I. Oligomers of alamethicin synthesized to control the aggregation state of the peptide ion channel. 

Fig. 3. (a) Chemical stmcture of a synthetic cycHc peptide composed of an alternating sequence of D- and L-amino acids. The side chains of the amino acids have been chosen such that the peripheral functional groups of the dat rings are hydrophobic and allow insertion into Hpid bilayers, (b) Proposed stmcture of a self-assembled transmembrane pore comprised of hydrogen bonded cycHc peptides. The channel is stabilized by hydrogen bonds between the peptide backbones of the individual molecules. These synthetic pores have been demonstrated to form ion channels in Hpid bilayers (71). 

Protein-protein interaction domain that binds to short peptide motif at the C-terminal of target proteins. Particularly important in spatial organization of receptors and ion channels. 

Several hundred species of Conus snails produce a wide array of small (12-30 AA) and mostly tightly disulfide bonded peptide ligands with high affinity for a diverse set of receptor and ion channel types. 

---