A cell-penetrating peptide derived from mammalian cell uptake protein of Mycobacterium tuberculosis

Analytical Biochemistry
Sangwei LuLee W Riley

Abstract

A Mycobacterium tuberculosis membrane protein called Mycobacterium cell entry protein (Mce1A) was previously shown to mediate the uptake of nonpathogenic Escherichia coli and latex beads by nonphagocytic mammalian cells. Here we characterize further the in vitro invasive activity of Mce1A using colloidal gold nanoparticles and fluorescent latex microspheres. Mce1A-coated colloidal gold particles induced plasma membrane invagination and entered membrane-bound compartments inside HeLa cells. Few of the protein-coated particles were also found in the cytosol compartment. Cytochalasin D and nocodazole inhibited the uptake by HeLa cells, indicating that rearrangement of both microtubules and microfilaments was necessary for the uptake. The functional domain of Mce1A for invasion was narrowed to a highly basic 22-amino acid sequence termed Inv3. A synthetic Inv3 peptide stimulated uptake of colloidal gold particles as well as latex microspheres by HeLa cells. A chimeric protein composed of Inv3 sequence at the N terminus of beta-galactosidase appeared to stain the nuclear membrane, suggesting that it entered the HeLa cell cytoplasm. These observations suggest that the cell uptake activity of Mce1A is confined to a small peptide domai...Continue Reading

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Citations

Sep 23, 2008·Journal of Materials Science. Materials in Medicine·Deendayal MandalGobinda Sarkar
Aug 13, 2014·Canadian Journal of Microbiology·Shantal Lizbeth Baltierra-UribeBlanca Estela García-Pérez
Apr 3, 2012·Drug Discovery Today·Francesca Milletti
Mar 2, 2010·Pharmaceuticals·Melaine Delcroix, Lee W Riley
Oct 16, 2015·PloS One·Sofie StalmansBart De Spiegeleer
Oct 29, 2008·The Journal of Biological Chemistry·William W MohnLindsay D Eltis
Feb 25, 2014·ACS Nano·Dana Maria CopoloviciÜlo Langel

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