Epitope and Paratope Mapping Reveals Temperature-Dependent Alterations in the Dengue-Antibody Interface.

Lim XX, Chandramohan A, Lim XE, Crowe JE, Lok SM, Anand GS
Structure. 2017 25 (9): 1391-1402.e3

PMID: 28823471 · DOI:10.1016/j.str.2017.07.007

Uncovering mechanisms of antibody-mediated neutralization for viral infections requires epitope and paratope mapping in the context of whole viral particle interactions with the antibody in solution. In this study, we use amide hydrogen/deuterium exchange mass spectrometry to describe the interface of a dengue virus-neutralizing antibody, 2D22, with its target epitope. 2D22 binds specifically to DENV2, a serotype showing strain-specific structural expansion at human host physiological temperatures of 37°C. Our results identify the heavy chain of 2D22 to be the primary determinant for binding DENV2. Temperature-mediated expansion alters the mode of interaction of 2D22 binding. Importantly, 2D22 interferes with the viral expansion process and offers a basis for its neutralization mechanism. The relative magnitude of deuterium exchange protection upon antibody binding across the various epitope loci allows a deconstruction of the antibody-viral interface in host-specific environments and offers a robust approach for targeted antibody engineering.

Copyright © 2017 Elsevier Ltd. All rights reserved.

MeSH Terms (14)

Antibodies, Neutralizing Antibodies, Viral Binding Sites, Antibody Dengue Virus Deuterium Exchange Measurement Epitope Mapping Epitopes Humans Mass Spectrometry Models, Molecular Protein Binding Protein Conformation Temperature Viral Envelope Proteins

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