A Membrane-Translocating Peptide Penetrates into Bilayers without Significant Bilayer Perturbations

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...

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Bibliographic Details
Published in:Biophysical journal 2013-06, Vol.104 (11), p.2419-2428
Main Authors: Cruz, Juan, Mihailescu, Mihaela, Wiedman, Greg, Herman, Katherine, Searson, Peter C., Wimley, William C., Hristova, Kalina
Format: Article
Language:English
Subjects:
binding properties
Biophysics
Cell Membrane - metabolism
Cells
HIV
Human immunodeficiency virus
lipid bilayers
Lipid Bilayers - metabolism
Lipids
Membrane
membrane permeability
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Membranes
Oligopeptides - chemistry
Oligopeptides - metabolism
peptide transporters
Peptides
Phosphatidylcholines - metabolism
Protein Structure, Secondary
Protein Transport
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Summary: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.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2013.04.043