title: A membrane-translocating peptide penetrates into bilayers without significant bilayer perturbations.
abstract: Using a high throughput screen, we have identified a family of 12-residue long peptides that spontaneously translocate across membranes. These peptides function by a poorly understood mechanism that is very different from that of the well-known, highly cationic cell penetrating peptides such as the tat peptide from HIV. The newly discovered translocating peptides can carry polar cargoes across synthetic bilayers and across cellular membranes quickly and spontaneously without disrupting the membrane. Here we report on the biophysical characterization of a representative translocating peptide from the selected family, TP2, as well as a negative control peptide, ONEG, from the same library. We measured the binding of the two peptides to lipid bilayers, their secondary structure propensities, their dispositions in bilayers by neutron diffraction, and the response of the bilayer to the peptides. Compared to the negative control, TP2 has a greater propensity for membrane partitioning, although it still binds only weakly, and a higher propensity for secondary structure. Perhaps most revealing, TP2 has the ability to penetrate deep into the bilayer without causing significant bilayer perturbations, a property that may help explain its ability to translocate without bilayer permeabilization.
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Cruz
authors.forename: Mihaela
authors.initials: M
authors.lastname: Mihailescu
authors.forename: Greg
authors.initials: G
authors.lastname: Wiedman
authors.forename: Katherine
authors.initials: K
authors.lastname: Herman
authors.forename: Peter C
authors.initials: PC
authors.lastname: Searson
authors.forename: William C
authors.initials: WC
authors.lastname: Wimley
authors.forename: Kalina
authors.initials: K
authors.lastname: Hristova
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D017433:Protein Structure, Secondary; D021381:Protein Transport
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D009842:Oligopeptides; D010713:Phosphatidylcholines; C028694:1-palmitoyl-2-oleoylphosphatidylcholine