Document Type
Article
Publication Date
7-1-2010
Abstract
LDL mediates transfection with plasmid DNA in a variety of cell types in vitro and in several tissues in vivo in the rat. The transfection capacity of LDL is based on apo B100, as arginine/lysine clusters, suggestive of nucleic acid-binding domains and nuclear localization signal sequences, are present throughout the molecule. Apo E may also contribute to this capacity because of its similarity to the Dengue virus capsid proteins and its ability to bind DNA. Synthetic peptides representing two apo B100 regions with prominent Arg/Lys clusters were shown to bind DNA. Region 1 (0014Lys-Ser 0160) shares sequence motifs present in DNA binding domains of Interferon Regulatory Factors and Flaviviridae capsid/core proteins. It also contains a close analog of the B/E receptor ligand of apo E. Region 1 peptides, B1-1 (0014Lys-Glu0054) and B1-2 (0055Leu- Ala0096), mediate transfection of HeLa cells but are cytotoxic. Region 2 (3313Asp-Thr3431), containing the known B/E receptor ligand, shares analog motifs with the human herpesvirus 5 immediate-early transcriptional regulator ( UL122) and Flaviviridae NS3 helicases. Region 2 peptides, B2-1 (3313Asp-Glu3355), and B2-2 (3356Gly-Thr3431) are ineffective in cell transfection and are noncytotoxic.jlr These results confirm the role of LDL as a natural transfection vector in vivo, a capacity imparted by the apo B100, and suggest a basis for Flaviviridae cell entry. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.
Recommended Citation
Guevara, J., Prashad, N., Ermolinsky, B., Gaubatz, J. W., Kang, D., Schwarzbach, A. E., ... & Guevara, N. V. (2010). Apo B100 similarities to viral proteins suggest basis for LDL-DNA binding and transfection capacity. Journal of lipid research, 51(7), 1704-1718. http://doi.org/10.1194/jlr.M003277
First Page
1704
Last Page
1718
Publication Title
Journal of Lipid Research
DOI
10.1194/jlr.M003277
Comments
This research was originally published in the Journal of Lipid Research. Juan Guevara Jr., Nagindra Prashad, Boris Ermolinsky, John W. Gaubatz, Dongcheul Kang, Andrea E. Schwarzbach, David S. Loose, and Natalia Valentinova Guevara. Apo B100 similarities to viral proteins suggest basis for LDL-DNA binding and transfection capacity. J. Lipid Res. 2010; 51:1704-1718. © the American Society for Biochemistry and Molecular Biology or © the Author(s).