The art of blocking ARTs: Nanobodies as experimental and therapeutic tools to block mammalian and toxin ADP-ribosyltransferases

MENZEL S, RISSIEK B, HAAG F, GOLDBAUM F AND KOCH-NOLTE F.

FEBS JOURNAL

WILEY-BLACKWELL PUBLISHING, INC

Año: 2013 vol. 15 p. 3543 - 3550

1742-464X

In 1901, the first Nobel Prize in Physiology or Medicine was awarded to Emil von Behring for his ground-breaking discovery of serum therapy: serum from horses vaccinated with toxin-containing culture medium of Corynebacterium diphtheriae contained life-saving ´antitoxins´. The molecular nature of the ADP-ribosylating toxin and the neutralizing antibodies were unraveled only 50 years later. Today, von Behring´s antibody therapy is being refined with a new generation of recombinant antibodies and antibody fragments. Nanobodies, which are single-domain antibodies derived from the peculiar heavy-chain antibodies of llamas and other camelids, are emerging as a promising new class of highly specific enzyme inhibitors. In this review, we illustrate the potential of nanobodies as tools to block extracellular and intracellular ADP-ribosyltransferases (ARTs), using the toxin-related membrane-bound mammalian ecto-enzyme ARTC2 and the actin-ADP-ribosylating Salmonella virulence plasmid factor B toxin of Salmonella enterica as examples.