New and Notable And Yet It Moves

Abstract

E pur si muove (and yet it moves) is a comment attributed to Galileo after the Catholic Church forced him to recant his theory that the earth moved around the sun. In this issue of the Biophysical Journal, Fuselier and Wimley (1) report the discovery of an amino acid sequence motif that appears to impart to polypeptides the ability to translocate across lipid membranes silently—that is, without causing flux of aqueous solutes across the membrane. This work follows a series of articles from Wimley’s laboratory on methods to reliably measure translocation of membraneactive peptides across phospholipid membranes, and on the use of an orthogonal high-throughput assay to screen combinatorial libraries of membrane-active peptides to specifically select for those peptides that spontaneously translocate but do not permeabilize membranes to water-soluble molecules (2–4). The translocating peptide TP2 emerged from this selection procedure as one of the most effective (2). TP2 is a 13-residue cationic peptide with the sequence PLIYLRLLRGQWC-amide. It was shown to cross the membranes of lipid vesicles and cells, even with polar fluorescent dyes attached (2,5). Wimley and co-workers noticed that the central