ArticleCommunications biology2023
VHH CDR-H3 conformation is determined by VH germline usage.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Integrative Modeling in the Age of Machine Learning: A Summary of HADDOCK Strategies in CAPRI Rounds 47-55.Proteins · 2026Article
- Combining AI Structure Prediction and Integrative Modeling for Nanobody-Antigen Complexes.Journal of chemical information and modeling · 2026Article
- Convergent strategies for nanobody-mediated inhibition of an epoxide hydrolase.bioRxiv : the preprint server for biology · 2026Article
- Disulphide and sequence-encoded conformational priors guide nanobody structure prediction.bioRxiv : the preprint server for biology · 2026Article
- Characterising nanobody developability to improve therapeutic design using the Therapeutic Nanobody Profiler.Communications biology · 2026Article
- Targeting angiogenesis: advances in the design and engineered applications of nanobodies.Frontiers in immunology · 2026Review
- Review
- Computational Prediction of Single-Domain Immunoglobulin Aggregation Propensities Facilitates Discovery and Humanization of Recombinant Nanobodies.Antibodies (Basel, Switzerland) · 2025Article
- Pathogen-specific kinetics of oxidative burst in camel leukocytes: Influence of serum opsonization on reactive oxygen species production.Veterinary world · 2025Article
- Optimization of a sarbecovirus llama nanobody-antigen binding interface via a combined computational and phage display protein engineering approach.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Highly Potent Neutralizing Nanobodies Acting Against Chikungunya Virus Infection via Inhibiting Multiple Stages of the Viral Life Cycle.International journal of molecular sciences · 2025Article
- Protein sequence modelling with Bayesian flow networks.Nature communications · 2025Article
- Affinity-stability trade-off mechanism of residue 35 in framework region 2 of VProtein science : a publication of the Protein Society · 2025Article
- Nanobody engineering: computational modelling and design for biomedical and therapeutic applications.FEBS open bio · 2025Review
- Comparative analysis of CDR3 length-dependent patterns in VHHs.Frontiers in immunology · 2025Article
- On the humanization of VHHs: Prospective case studies, experimental and computational characterization of structural determinants for functionality.Protein science : a publication of the Protein Society · 2024Article
- Phage display-derived alpaca nanobodies as potential therapeutics forApplied and environmental microbiology · 2024Article
- De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics.ACS chemical biology · 2024Article
- Distinct types of VHHs in Alpaca.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VHHs or nanobodies are single antigen binding domains originating from camelid heavy-chain antibodies. They are used as diagnostic and research tools and in a variety of therapeutic molecules. Analyzing variable domain structures from llama and alpaca we found that VHHs can be classified into two large structural clusters based on their CDR-H3 conformation. Extended CDR-H3 loops protrude into the solvent, whereas kinked CDR-H3 loops fold back onto framework regions. Both major families have distinct properties in terms of their CDR-H3 secondary structure, how their CDR-H3 interacts with the framework region and how they bind to antigens. We show that the CDR-H3 conformation of VHHs correlates with the germline from which the antibodies are derived: IGHV3-3 derived antibodies almost exclusively adopt a kinked CDR-H3 conformation while the CDR-H3 adopts an extended structure in most IGHV3S53 derived antibodies. We do not observe any bias stemming from V(D)J recombination in llama immune repertoires, suggesting that the correlation is the result of selection processes during B-cell development. Our findings demonstrate a previously undescribed impact of germline usage on antigen interaction and contribute to a better understanding on how properties of the antibody framework shape the immune repertoire.
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