Prediction of a conserved, neutralizing epitope in ribosome-inactivating proteins

The secondary structures, side-chain solvent accessibilities, and superposi tioned crystal structures of the A-chain of ricin and four other plant rRNA N-glycosidases (ribosome-inactivating proteins, RIPs) were examined. Previ ously, a 26-residue fragment from the A-chain of ricin was determined to bi nd to a neutralizing monoclonal antibody. The region in the native ricin A- chain, to which this peptide corresponds, is solvent-exposed and contains a negatively charged residue that has been hypothesized to participate in th e toxin's function, namely, rRNA binding and/of enzymatic activity. This re gion appears to be conserved in all of the structurally defined plant RIPs examined. Moreover, other plant RIPs, whose tertiary structures are, as yet , unknown, were predicted to have an analogous, solvent-exposed region cont aining a conserved, negatively charged residue. By analogy, these conserved structural and functional features lead to the suggestion that this er;pos ed region represents a logical starting point for experiments designed to l ocate neutralizing epitopes in these RIPs. In contrast, the tertiary struct ure of the analogous region in a bacteria-derived RIP (Shiga toxin) is a le ss solvent-exposed, truncated loop and is a structure that is not as likely to be a neutralizing epitope. Because most of the amino acid residues are not conserved within this exposed region, these RIPs are predicted to be an tigenically distinct. (C) 1999 Published by Elsevier Science B.V. All right s reserved.