Understanding mechanisms underlying ricin toxin neutralization aids rational design of vaccines

X-ray Crystal Structures of Ricin Toxin in Complex with Neutralizing and Non-neutralizing antibodies

In collaboration with researchers at the Wadsworth Center, NYSBC crystallographers solved the crystal structures of the ricin enzymatic subunit in complex with the antigen binding domain of several single-chain monoclonal antibodies. Ricin is a well-known biothreat agent that has been the focus of an ongoing vaccine-development effort for use by military personnel and at-risk civilians.

X-ray crystal structures guide a more rational vaccine design.

X-ray crystal structures of neutralizing (G12) and non-neutralizing (A7) antibodies bound to the enzymatic subunit of ricin revealed key molecular details that influence ricin neutralization. A comparison of the binding modes of these two antibodies to the ricin catalytic subunit illustrates differences caused by the presence of a proline residue at position 106 in A7. This proline residue minimizes the interaction between A7 and the ricin catalytic subunit relative to G12 by removing three key hydrogen bonds. This difference likely contributes to A7’s inability to neutralize ricin. This information can be utilized to design a more effective vaccine against the ricin toxin.

Research article:
Journal of Molecular Biology, June 2014
PMID: 24907552
DOI: 10.1016/j.jmb.2014.05.026