The DOI matches its Crossref record; 87 of the 87 references it cites were found in a registry or an index.
Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies
Abstract
Truncated versions of heavy-chain antibodies (HCAbs) from camelids, also termed nanobodies, comprise only one-tenth the mass of conventional antibodies, yet retain similar, high binding affinities for the antigens. Here we analyze a large data set of nanobody-antigen crystal structures and investigate how nanobody-antigen recognition compares to the one by conventional antibodies. We find that nanobody paratopes are enriched in aromatic residues just like conventional antibodies, but additionally, they also bear a more hydrophobic character. Most striking differences were observed in the characteristics of the antigen's epitope. Unlike conventional antibodies, nanobodies bind to more rigid, concave, conserved and structured epitopes enriched with aromatic residues. Nanobodies establish fewer interactions with the antigens compared to conventional antibodies, and we speculate that high binding affinities are achieved due to less unfavorable conformational and more favorable solvation entropy contributions. We observed that interactions with antigen are mediated not only by three CDR loops but also by numerous residues from the nanobody framework. These residues are not distributed uniformly; rather, they are concentrated into four structurally distinct regions and mediate mostly charged interactions. Our findings suggest that in some respects nanobody-antigen interactions are more similar to the general protein-protein interactions rather than antibody-antigen interactions.
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“The extended CDR3 loop of nanobodies has the capacity to form a finger-like structure with greater structural flexibility which, in turn, is likely fixed in one single conformation upon antigen-binding [14,15].”
From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [14]
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The therapeutic potential of nanobodies
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NANOBODIES®: A Review of Diagnostic and Therapeutic Applications
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A guide to: generation and design of nanobodies
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Muyldermans, S. (2020) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-021419-083831 · Cited by 350
Immunogenicity and humanization of single‐domain antibodies
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Metadata
- Authors
- Zavrtanik, U., Lukan, J., Loris, R., Lah, J., & Hadži, S.
- Affiliations
- University of Ljubljana (SI)
- Statistical Office of the Republic of Slovenia (SI)
- Vrije Universiteit Brussel (BE)
- Corresponding author
- Hadži, San
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 430
- Issue
- 21
- Pages
- 4369-4386
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2891129333
- Cited by
- 169
- References
- 87
- Citations by year
- 2026: 21 · 2025: 25 · 2024: 26 · 2023: 30 · 2022: 22 · 2021: 19 · 2020: 12 · 2019: 14
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Slovenian Research Agency (P1-0201)
- Onderzoeksraad of the Vrije Universiteit Brussel (SPR13)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- nanobodies, heavy-chain antibodies, camelid antibodies, epitope recognition, antibody binding sites, aromatic residues, hydrophobic interactions, CDR loops, binding affinity, solvation entropy, protein-protein interaction, crystal structure
- MeSH terms
- Camelidae, Animals, Epitopes, Binding Sites, Binding Sites, Antibody, Camelids, New World, Immunoglobulin Heavy Chains, Models, Molecular, Protein Binding, Crystallography, X-Ray, Single-Domain Antibodies
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