Comparative analysis of CDR3 length-dependent patterns in VHHs Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.3389/fimmu.2025.1647230
Introduction VHHs, or nanobodies, are distinguished by their compact size, high stability, and unique ability to selectively target specific epitopes. The CDR3 region in VHHs, which plays a crucial role in antigen binding, exhibits significant diversity and varies among species. Method This study systematically examined CDR3 length dependent patterns by analyzing NGS sequences from the PBMCs of Alpacas, Llamas and Bactrians, in conjunction with VHH structure data from the public database. Results VHHs from Alpacas and Llamas exhibited similar CDR3 length distributions, while Bactrian VHHs displayed significantly longer but narrower length distribution. Key sequence, structural, and VHH/antigen interaction characteristics correlated with CDR3 length were identified. Specifically, longer CDR3s were associated with a lower net charge, reduced surface hydrophobicity, and enhanced interactions with other VHH regions. Structural analyses revealed that longer CDR3s tended to adopt bent conformations with increased helical and coil structures, whereas shorter CDR3s favored extended conformations and β-sheets. Associations between CDR3 length and amino acid usage patterns within VHH sequences were also observed, including preferences at various sites and in antigen interactions. Notably, species-specific differences were apparent, with Alpaca and Llama VHHs showing more pronounced CDR3 length-dependent patterns than those from Bactrians. Discussion These findings highlight the significant impact of CDR3 length on VHH sequence, structure, and antigen interaction characteristics, providing valuable insights for VHH engineering, synthetic library design, and the development of therapeutic nanobodies optimized for targeting diverse epitopes.
Related Topics
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2025.1647230
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1647230/pdf
- OA Status
- gold
- Cited By
- 1
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413381313
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4413381313Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2025.1647230Digital Object Identifier
- Title
-
Comparative analysis of CDR3 length-dependent patterns in VHHsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-08-15Full publication date if available
- Authors
-
Lu Zhang, Tianyu Yang, Yao Zhang, Jiahui Yan, Jiaguo Li, Wenfeng Xu, Weimin Zhu, Xinhao WangList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2025.1647230Publisher landing page
- PDF URL
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https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1647230/pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1647230/pdfDirect OA link when available
- Concepts
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Epitope, Complementarity determining region, Biology, Computational biology, Single-domain antibody, Random coil, Antigen, Genetics, Antibody, Peptide sequence, Gene, Biochemistry, Protein secondary structureTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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43Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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