Structural Analysis of Single Domain Antibodies Bound to a Second Neutralizing Hot Spot on Ricin Toxin's Enzymatic Subunit.

ABSTRACT: Ricin toxin is a heterodimer consisting of RTA, a ribosome-inactivating protein, and RTB, a lectin that facilitates receptor-mediated uptake into mammalian cells. In previous studies, we demonstrated that toxin-neutralizing antibodies target four spatially distinct hot spots on RTA, which we refer to as epitope clusters I-IV. In this report, we identified and characterized three single domain camelid antibodies (V_HH) against cluster II. One of these V_HHs, V5E1, ranks as one of the most potent ricin-neutralizing antibodies described to date. We solved the X-ray crystal structures of each of the three V_HHs (E1, V1C7, and V5E1) in complex with RTA. V5E1 buries a total of 1,133 Ų of surface area on RTA and makes primary contacts with α-helix A (resi

SUBMITTER: Rudolph MJ 

PROVIDER: S-EPMC5247660 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature