title: Engineering a Transmembrane Nanopore Ion Channel from a Membrane Breaker Peptide.
abstract: Re-engineering nature's molecules is an ideal strategy to obtain explicit functionality such as synthetic molecular machines, yet novel strategies for producing engineered molecular channels are few. Here we report a peptide engineering strategy through sequence reversal, which we applied on the first transmembrane peptide of the mycobacteriophage membranoporin protein holin. We have successfully redesigned the membrane rupture property of this peptide to form specific nanopore ion channels. We report the structural characterization and electrophysiology measurements of a library of 28-residue engineered membrane peptides, with remarkable ion channel behavior. We further identify that key residues at the peptide terminus, the central proline, charge distribution, and hydropathy index of the peptide together contribute to the channel properties that we measure. Our sequence reversal strategy for peptide engineering to successfully obtain nanopore channels can pave the way for better biobased design of controlled nanopores, using only natural amino acids.
authors.affiliation: Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research , ITI Building, Govindpura, Bhopal - 462023, India.
authors.forename: Muralikrishna
authors.initials: M
authors.lastname: Lella
authors.affiliation: Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research , ITI Building, Govindpura, Bhopal - 462023, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahalakshmi
mesh_terms: D000595:Amino Acid Sequence; D007473:Ion Channels / Q000737:chemistry*; D058608:Nanopores; D010455:Peptides / Q000737:chemistry*; D015202:Protein Engineering
chemical_list: D007473:Ion Channels; D010455:Peptides