title: A synthetic peptide forms voltage-gated porin-like ion channels in lipid bilayer membranes.
abstract: Design of simple protein structures represents the essential first step toward novel macromolecules and understanding the basic principles of protein folding. Our work focuses on the ion channel formation and structure of peptides having a repeated pattern of glycine residues. Investigation of the ion channel properties of a glycine repeat peptide, VSLGLSIGFSVGVSIGWSFGRSRG revealed the formation of porin-like high conductance, multimeric, non-selective voltage-gated channels in phospholipid bilayer membranes. ATR-IR and CD spectroscopic studies showed an anti-parallel beta sheet structure in membranes. The formation of porin-like ion channels by a beta sheet peptide suggests spontaneous assembly into a beta barrel structure through oligomerization as in pore forming bacterial toxins. The present work is the first example of a short synthetic peptide mimicking the pore characteristics of a complex beta barrel protein and demonstrates that smaller peptides are capable of mimicking the complex functional properties of natural ion channels. This will have implications in understanding the folding of beta sheet proteins in membranes, the mechanism of two state voltage gating, and the role of glycine residues in beta barrel proteins.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Thundimadathil
authors.forename: Roger W
authors.initials: RW
authors.lastname: Roeske
authors.forename: Lili
authors.initials: L
authors.lastname: Guo
mesh_terms: D000595:Amino Acid Sequence; D015640:Ion Channel Gating; D007473:Ion Channels / Q000138:chemical synthesis*; D008051:Lipid Bilayers; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D018272:Porins / Q000138:chemical synthesis*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D010455:Peptides; D018272:Porins