title: Peptide aptamer-mediated inhibition of target proteins by sequestration into aggresomes.
abstract: Peptide aptamers (PAs) can be employed to block the intracellular function of target proteins. Little is known about the mechanism of PA-mediated protein inhibition. Here, we generated PAs that specifically bound to the duck hepatitis B virus (HBV) core protein. Among them, PA34 strongly blocked duck HBV replication by inhibiting viral capsid formation. We found that PA34 led to a dramatic intracellular redistribution of its target protein into perinuclear inclusion bodies, which exhibit the typical characteristics of aggresomes. As a result, the core protein is efficiently removed from the viral life cycle. Corresponding findings were obtained for bioactive PAs that bind to the HBV core protein or to the human papillomavirus-16 (HPV16) E6 protein, respectively. The observation that PAs induce the specific sequestration of bound proteins into aggresomes defines a novel mechanism as to how this new class of intracellular inhibitors blocks the function of their target proteins.
authors.affiliation: Molecular Therapy of Virus-Associated Cancers Group (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Tomai
authors.affiliation: Molecular Therapy of Virus-Associated Cancers Group (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Butz
authors.affiliation: Molecular Therapy of Virus-Associated Cancers Group (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lohrey
authors.affiliation: Medizinische Universitätsklinik II, D-79106 Freiburg, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: von Weizsäcker
authors.affiliation: Electron Microcopy Group (F090), German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.affiliation: Molecular Therapy of Virus-Associated Cancers Group (F065), German Cancer Research Center, D-69120 Heidelberg, Germany. Electronic address: hoppe-seyler@dkfz.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Hoppe-Seyler
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D052158:Aptamers, Peptide / Q000737:chemistry*; D045744:Cell Line, Tumor; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins / Q000378:metabolism; D014746:Vimentin / Q000737:chemistry; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D052158:Aptamers, Peptide; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D010455:Peptides; D011506:Proteins; D012097:Repressor Proteins; D014746:Vimentin