Stability convergence in natural antibodies with ultra-long hypervariable loops Article Swipe
Marcel Passon
,
Matja Zalar
,
Thomas Nehls
,
Stefaan C. De Smedt
,
Frederik Lermyte
,
Ahmad Reza Mehdipour
,
Hristo L. Svilenov
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s42003-025-08036-5
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s42003-025-08036-5
Antibodies bind to antigens with hypervariable loops called complementarity-determining regions (CDRs). In contrast to conventional antibodies, a subset of bovine antibodies has an ultra-long CDR (ulCDR) composed of up to 70 residues folded as a stalk and knob. The fundamental principles of how these antibodies maintain their structure and stability remain enigmatic. Here, we investigated how different natural ulCDRs affect antibody structure, stability and function. To this end, we swapped diverse ulCDRs onto the same antibody scaffold. All ulCDR-swap variants exhibit nearly identical secondary structure fingerprints and remarkably similar thermal stability. In addition, specificity and high-affinity binding to the antigens are maintained. Hydrogen-deuterium exchange and molecular dynamics simulations suggest small differences between the variants arising from changed interactions between different stalks and the underlying scaffold. Overall, we reveal principles of grafting natural ulCDRs onto a common Fab scaffold, which have implications for antibody design for biomedical applications.
Related Topics
Concepts
Antibody
Complementarity determining region
Hypervariable region
Chemistry
Biophysics
Antigen
Biology
Computational biology
Monoclonal antibody
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s42003-025-08036-5
- https://www.nature.com/articles/s42003-025-08036-5.pdf
- OA Status
- gold
- Cited By
- 1
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409598624
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409598624Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s42003-025-08036-5Digital Object Identifier
- Title
-
Stability convergence in natural antibodies with ultra-long hypervariable loopsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-04-19Full publication date if available
- Authors
-
Marcel Passon, Matja Zalar, Thomas Nehls, Stefaan C. De Smedt, Frederik Lermyte, Ahmad Reza Mehdipour, Hristo L. SvilenovList of authors in order
- Landing page
-
https://doi.org/10.1038/s42003-025-08036-5Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s42003-025-08036-5.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://www.nature.com/articles/s42003-025-08036-5.pdfDirect OA link when available
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Antibody, Complementarity determining region, Hypervariable region, Chemistry, Biophysics, Antigen, Biology, Computational biology, Monoclonal antibody, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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58Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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