title: Natural intracellular peptides can modulate the interactions of mouse brain proteins and thimet oligopeptidase with 14-3-3ε and calmodulin.
abstract: Protein interactions are crucial for most cellular process. Thus, rationally designed peptides that act as competitive assembly inhibitors of protein interactions by mimicking specific, determined structural elements have been extensively used in clinical and basic research. Recently, mammalian cells have been shown to contain a large number of intracellular peptides of unknown function. Here, we investigate the role of several of these natural intracellular peptides as putative modulators of protein interactions that are related to Ca(2+) -calmodulin (CaM) and 14-3-3ε, which are proteins that are related to the spatial organization of signal transduction within cells. At concentrations of 1-50 μM, most of the peptides that are investigated in this study modulate the interactions of CaM and 14-3-3ε with proteins from the mouse brain cytoplasm or recombinant thimet oligopeptidase (EP24.15) in vitro, as measured by surface plasmon resonance. One of these peptides (VFDVELL; VFD-7) increases the cytosolic Ca(2+)  concentration in a dose-dependent manner but only if introduced into HEK293 cells, which suggests a wide biological function of this peptide. Therefore, it is exciting to suggest that natural intracellular peptides are novel modulators of protein interactions and have biological functions within cells.
authors: Department of Cell Biology and Development, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
authors: Lilian C
authors: LC
authors: Russo
authors: Amanda F
authors: AF
authors: Asega
authors: Leandro M
authors: LM
authors: Castro
authors: Priscilla D
authors: PD
authors: Negraes
authors: Lilian
authors: L
authors: Cruz
authors: Fabio C
authors: FC
authors: Gozzo
authors: Henning
authors: H
authors: Ulrich
authors: Antonio C M
authors: AC
authors: Camargo
authors: Vanessa
authors: V
authors: Rioli
authors: Emer S
authors: ES
authors: Ferro
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D060066:Protein Interaction Maps; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D002147:Calmodulin; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C022510:thimet oligopeptidase; D002118:Calcium