Peptide aptamer-mediated inhibition of target proteins by sequestration into aggresomes |
| |
Authors: | Tomai Evangelia Butz Karin Lohrey Claudia von Weizsäcker Fritz Zentgraf Hanswalter Hoppe-Seyler Felix |
| |
Institution: | Molecular Therapy of Virus-Associated Cancers Group (F065), German Cancer Research Center, Heidelberg. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|