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dc.contributor.authorAngalakurthi, Siva Krishna
dc.contributor.authorVance, David J.
dc.contributor.authorRong, Yinghui
dc.contributor.authorNguyen, Chi My Thi
dc.contributor.authorRudolph, Michael J.
dc.contributor.authorVolkin, David
dc.contributor.authorMiddaugh, C. Russell
dc.contributor.authorWeis, David D.
dc.contributor.authorMantis, Nicholas J.
dc.date.accessioned2020-11-25T15:03:38Z
dc.date.available2020-11-25T15:03:38Z
dc.date.issued2018-12-17
dc.identifier.citationAngalakurthi, S. K., Vance, D. J., Rong, Y., Nguyen, C., Rudolph, M. J., Volkin, D., Middaugh, C. R., Weis, D. D., & Mantis, N. J. (2018). A Collection of Single-Domain Antibodies that Crowd Ricin Toxin's Active Site. Antibodies (Basel, Switzerland), 7(4), 45. https://doi.org/10.3390/antib7040045en_US
dc.identifier.urihttp://hdl.handle.net/1808/30926
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractIn this report, we used hydrogen exchange-mass spectrometry (HX-MS) to identify the epitopes recognized by 21 single-domain camelid antibodies (VHHs) directed against the ribosome-inactivating subunit (RTA) of ricin toxin, a biothreat agent of concern to military and public health authorities. The VHHs, which derive from 11 different B-cell lineages, were binned together based on competition ELISAs with IB2, a monoclonal antibody that defines a toxin-neutralizing hotspot (“cluster 3”) located in close proximity to RTA’s active site. HX-MS analysis revealed that the 21 VHHs recognized four distinct epitope subclusters (3.1–3.4). Sixteen of the 21 VHHs grouped within subcluster 3.1 and engage RTA α-helices C and G. Three VHHs grouped within subcluster 3.2, encompassing α-helices C and G, plus α-helix B. The single VHH in subcluster 3.3 engaged RTA α-helices B and G, while the epitope of the sole VHH defining subcluster 3.4 encompassed α-helices C and E, and β-strand h. Modeling these epitopes on the surface of RTA predicts that the 20 VHHs within subclusters 3.1–3.3 physically occlude RTA’s active site cleft, while the single antibody in subcluster 3.4 associates on the active site’s upper rim.en_US
dc.description.sponsorshipNational Institutes of Allergy and Infectious Diseases, National Institutes of Health (HHSN272201400021C)en_US
dc.publisherMDPIen_US
dc.rights© 2018 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectToxinen_US
dc.subjectAntibodyen_US
dc.subjectCameliden_US
dc.subjectVaccineen_US
dc.subjectBiodefenseen_US
dc.subjectHydrogen exchange-mass spectrometryen_US
dc.titleA Collection of Single-Domain Antibodies that Crowd Ricin Toxin’s Active Siteen_US
dc.typeArticleen_US
kusw.kuauthorAngalakurthi, Siva Krishna
kusw.kuauthorVolkin, David
kusw.kuauthorMiddaugh, C. Russell
kusw.kuauthorWeis, David D.
kusw.kudepartmentPharmaceutical Chemistryen_US
kusw.kudepartmentChemistryen_US
dc.identifier.doi10.3390/antib7040045en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-9913-7722en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-3032-1211en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-5083-8640en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC6374049en_US
dc.rights.accessrightsopenAccessen_US


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© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Except where otherwise noted, this item's license is described as: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.