Peptide aptamer-mediated inhibition of target proteins by sequestration into aggresomes
Peptide aptamer-mediated inhibition of target proteins by sequestration into aggresomes
May 2006
Evangelia Tomai, Karin Butz, Claudia Lohrey, Fritz von Weizs?cker, Hanswalter Zentgraf, and Felix Hoppe-Seyler
J. Biol. Chem
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 which specifically bound to the duck hepatitis B virus (DHBV) core protein. Among them, PA34 strongly blocked DHBV 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 which bind to the hepatitis B virus (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.
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