6OBO

Ricin A chain bound to VHH antibody V6A6

Summary for 6OBO

• Entry DOI: 10.2210/pdb6obo/pdb
• Descriptor: Ricin A chain, VHH antibody V6A6, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: toxin
• Biological source: Ricinus communis (Castor bean); More
• Total number of polymer chains: 4
• Total formula weight: 84224.03

Authors

Rudolph, M.J. (deposition date: 2019-03-21, release date: 2020-04-01, Last modification date: 2024-10-23)

Primary citation

Rudolph, M.J.,Czajka, T.F.,Davis, S.A.,Thi Nguyen, C.M.,Li, X.P.,Tumer, N.E.,Vance, D.J.,Mantis, N.J.
Intracellular Neutralization of Ricin Toxin by Single-domain Antibodies Targeting the Active Site.
J.Mol.Biol., 432:1109-1125, 2020

PubMed Abstract: The extreme potency of the plant toxin, ricin, is due to its enzymatic subunit, RTA, which inactivates mammalian ribosomes with near-perfect efficiency. Here we characterized, at the functional and structural levels, seven alpaca single-domain antibodies (VHs) previously reported to recognize epitopes in proximity to RTA's active site. Three of the VHs, V2A11, V8E6, and V2G10, were potent inhibitors of RTA in vitro and protected Vero cells from ricin when expressed as intracellular antibodies ("intrabodies"). Crystal structure analysis revealed that the complementarity-determining region 3 (CDR3) elements of V2A11 and V8E6 penetrate RTA's active site and interact with key catalytic residues. V2G10, by contrast, sits atop the enzymatic pocket and occludes substrate accessibility. The other four VHs also penetrated/occluded RTA's active site, but lacked sufficient binding affinities to outcompete RTA-ribosome interactions. Intracellular delivery of high-affinity, single-domain antibodies may offer a new avenue in the development of countermeasures against ricin toxin.toxin, antibody, structure, intracellular.

PubMed: 31931008
DOI: 10.1016/j.jmb.2020.01.006

Experimental method

X-RAY DIFFRACTION (1.9 Å)