Cell penetrating peptides and cationic antibacterial peptides: two sides of the same coin

• Published in: The Journal of biological chemistry Vol. 289; no. 21; pp. 14448 - 14457
• Main Authors: Rodriguez Plaza, Jonathan G, Morales-Nava, Rosmarbel, Diener, Christian, Schreiber, Gabriele, Gonzalez, Zyanya D, Lara Ortiz, Maria Teresa, Ortega Blake, Ivan, Pantoja, Omar, Volkmer, Rudolf, Klipp, Edda, Herrmann, Andreas, Del Rio, Gabriel
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 23.05.2014
• Subjects: Algorithms; Amino Acid Sequence; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacokinetics; Antimicrobial Cationic Peptides - pharmacology; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - pharmacokinetics; Cell-Penetrating Peptides - pharmacology; Endocytosis - genetics; HEK293 Cells; Humans; Kinetics; Mating Factor; Microbial Viability - drug effects; Microbial Viability - genetics; Microbiology; Models, Biological; Molecular Sequence Data; Mutation; Peptides - chemistry; Peptides - pharmacokinetics; Peptides - pharmacology; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Membrane Biophysics; Receptor Endocytosis; Antimicrobial Peptides; Cell-penetrating Peptides; Computational Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.515023

Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs.