title: Structure and function correlation in histone H2A peptide-mediated gene transfer.
abstract: Histone H2A has been found to be efficient in DNA delivery into a number of cell lines. We have reasoned that this DNA-delivery activity is mediated by two mechanisms: (i) electrostatically driven DNA binding and condensation by histone and (ii) nuclear import of these histone H2A.DNA polyplexes via nuclear localization signals in the protein. We have identified a 37-aa N-terminal peptide of histone H2A that is active in in vitro gene transfer. This peptide can function as a nuclear localization signal and can bind DNA. Amino acid substitutions that replace positively charged residues and/or DNA-binding residues of this peptide obliterate transfection activity. The introduction of a proline in the first turn of an alpha-helix of this 37-mer obliterates transfection activity, suggesting that the integrity of the alpha-helical structure of the N-terminal region of histone H2A is related to its transfection activity.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM 215, La Jolla, CA 92037, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Balicki
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Putnam
authors.forename: Puthupparampil V
authors.initials: PV
authors.lastname: Scaria
authors.forename: Ernest
authors.initials: E
authors.lastname: Beutler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002522:Chlorocebus aethiops; D018014:Gene Transfer Techniques; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D014162:Transfection
chemical_list: D006657:Histones; D010446:Peptide Fragments; D011994:Recombinant Proteins