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The cyclic cystine knot miniprotein MCoTI-II is internalized into cells by macropinocytosis.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2007; Vol. 39 (12), pp. 2252-64. Date of Electronic Publication: 2007 Jul 07. - Publication Year :
- 2007
-
Abstract
- The cyclotides are macrocyclic knotted proteins characterized by a compact topology and exceptional stability. Accordingly it has been hypothesized that they may be useful as protein engineering frameworks for the stabilization and delivery of bioactive peptide sequences. This study examined the internalization of cyclotides into mammalian cells, a vital step for the delivery of bioactive peptide sequences to intracellular targets. Although the entry of various linear peptides into cells has been reported previously, this is the first report of internalization of a macrocyclic peptide. Cell uptake was examined for representatives of two cyclotide subfamilies; the first was MCoTI-II, a member of the trypsin inhibitor subfamily, which was internalized by a macrophage and breast cancer cell line and the second, the prototypic cyclotide kalata B1 from the Möbius subfamily, which remained extracellular. Biotin labeled MCoTI-II entered macrophages by macropinocytosis, resulting in vesicular encapsulation without trafficking to lysosomes for degradation. The ready uptake, coupled with low cytotoxicity, indicates that MCoTI-II has the potential to transport grafted bioactivities to intracellular targets, making it a potentially valuable framework in drug design applications.
- Subjects :
- Amino Acid Sequence
Animals
Biotinylation
Cell Line
Cell Line, Tumor
Cell Survival drug effects
Cyclotides chemistry
Cyclotides pharmacology
Dextrans metabolism
Endosomes chemistry
Endosomes metabolism
Humans
Lysosomal Membrane Proteins analysis
Lysosomes chemistry
Lysosomes metabolism
Macrophages cytology
Magnetic Resonance Spectroscopy
Membrane Proteins analysis
Microscopy, Fluorescence
Molecular Sequence Data
Momordica chemistry
Rhodamines metabolism
Seeds chemistry
Sequence Homology, Amino Acid
Temperature
Vesicular Transport Proteins analysis
Cyclotides metabolism
Macrophages metabolism
Pinocytosis physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1357-2725
- Volume :
- 39
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 17693122
- Full Text :
- https://doi.org/10.1016/j.biocel.2007.06.016