Cell penetrating peptides and cationic antibacterial peptides: two sides of the same coin.
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.
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.
Jonathan G
JG
Rodriguez Plaza
Materials science and biophysics department, Instituto de Ciencias Fisicas, Universidad Nacional Autónoma de México, Av. Universidad S/N, Col. Chamilpa, 62210 Cuernavaca, Morelos, México.
Rosmarbel
R
Morales-Nava
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.
Christian
C
Diener
Instituto de Biotecnología, Universidad Nacional Autónoma de México, A.P. 510-3, Colonia Miraval, Cuernavaca, Morelos, México 62250.
Gabriele
G
Schreiber
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.
Zyanya D
ZD
Gonzalez
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.
Maria Teresa
MT
Lara Ortiz
Materials science and biophysics department, Instituto de Ciencias Fisicas, Universidad Nacional Autónoma de México, Av. Universidad S/N, Col. Chamilpa, 62210 Cuernavaca, Morelos, México.
Ivan
I
Ortega Blake
Instituto de Biotecnología, Universidad Nacional Autónoma de México, A.P. 510-3, Colonia Miraval, Cuernavaca, Morelos, México 62250.
Omar
O
Pantoja
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.
Rudolf
R
Volkmer
Theoretische und Molekulare Biophysik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany.
Edda
E
Klipp
Theoretische und Molekulare Biophysik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany.
Andreas
A
Herrmann
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.
Gabriel
G
Del Rio
D000465:Algorithms; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004705:Endocytosis / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D000072235:Mating Factor; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D057846:Cell-Penetrating Peptides; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D000072235:Mating Factor
Antimicrobial Peptides; Cell-penetrating Peptides; Computational Biology; Membrane Biophysics; Receptor Endocytosis