Analysis of nanobody paratopes reveals greater diversity than classical antibodies.
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Authors
Mitchell, Laura S
Colwell, Lucy J
Publication Date
2018-07-01Journal Title
Protein Eng Des Sel
ISSN
1741-0126
Publisher
Oxford University Press (OUP)
Volume
31
Issue
7-8
Pages
267-275
Language
eng
Type
Article
Physical Medium
Print
Metadata
Show full item recordCitation
Mitchell, L. S., & Colwell, L. J. (2018). Analysis of nanobody paratopes reveals greater diversity than classical antibodies.. Protein Eng Des Sel, 31 (7-8), 267-275. https://doi.org/10.1093/protein/gzy017
Abstract
Nanobodies (Nbs) are a class of antigen-binding protein derived from camelid immune systems, which achieve equivalent binding affinities and specificities to classical antibodies (Abs) despite being comprised of only a single variable domain. Here, we use a data set of 156 unique Nb:antigen complex structures to characterize Nb-antigen binding and draw comparison to a set of 156 unique Ab:antigen structures. We analyse residue composition and interactions at the antigen interface, together with structural features of the paratopes of both data sets. Our analysis finds that the set of Nb structures displays much greater paratope diversity, in terms of the structural segments involved in the paratope, the residues used at these positions to contact the antigen and furthermore the type of contacts made with the antigen. Our findings suggest a different relationship between contact propensity and sequence variability from that observed for Ab VH domains. The distinction between sequence positions that control interaction specificity and those that form the domain scaffold is much less clear-cut for Nbs, and furthermore H3 loop positions play a much more dominant role in determining interaction specificity.
Keywords
Animals, Antigens, Crystallography, X-Ray, Antibody Specificity, Amino Acid Sequence, Protein Conformation, Models, Molecular, Single-Chain Antibodies
Sponsorship
BBSRC (1501548)
European Commission (631609)
Identifiers
External DOI: https://doi.org/10.1093/protein/gzy017
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284148
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