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

Jonathan G Rodriguez Plaza; Rosmarbel Morales-Nava; Christian Diener; Gabriele Schreiber; Zyanya D Gonzalez; Maria Teresa Lara Ortiz; Ivan Ortega Blake; Omar Pantoja; Rudolf Volkmer; Edda Klipp; Andreas Herrmann; Gabriel Del Rio

doi:10.1074/jbc.M113.515023

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

J Biol Chem. 2014 May 23;289(21):14448-57. doi: 10.1074/jbc.M113.515023. Epub 2014 Apr 5.

Affiliations

¹ From the Biochemistry and Structural Biology Department, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior S/N Ciudad Universitaria, 04510 México D.F., México.
² Materials science and biophysics department, Instituto de Ciencias Fisicas, Universidad Nacional Autónoma de México, Av. Universidad S/N, Col. Chamilpa, 62210 Cuernavaca, Morelos, México.
³ Instituto de Biotecnología, Universidad Nacional Autónoma de México, A.P. 510-3, Colonia Miraval, Cuernavaca, Morelos, México 62250.
⁴ Institut für Medizinische Immunologie, Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, 10117 Berlin and Leibniz-Institut für Molekulare Pharmakologie, Robert-Roessle Strasse 10, 13125 Berlin, Germany, and.
⁵ Theoretische und Molekulare Biophysik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany.
⁶ From the Biochemistry and Structural Biology Department, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior S/N Ciudad Universitaria, 04510 México D.F., México, gdelrio@ifc.unam.mx.

Abstract

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.

Keywords: Antimicrobial Peptides; Cell-penetrating Peptides; Computational Biology; Membrane Biophysics; Receptor Endocytosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
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

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Cell-Penetrating Peptides
Peptides
Saccharomyces cerevisiae Proteins
Mating Factor