Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features
The Observed Antibody Space provides the most abundant collection of annotated paired antibody variable domain sequences, thus offering a unique platform for the systematic investigation of the factors governing the pairing of antibody heavy and light chains. By examining a range of characteristics,...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2025.2507950 |
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| author | Clarissa A. Seidler Vera A. Spanke Jakob Gamper Alexander Bujotzek Guy Georges Klaus R. Liedl |
| author_facet | Clarissa A. Seidler Vera A. Spanke Jakob Gamper Alexander Bujotzek Guy Georges Klaus R. Liedl |
| author_sort | Clarissa A. Seidler |
| collection | DOAJ |
| description | The Observed Antibody Space provides the most abundant collection of annotated paired antibody variable domain sequences, thus offering a unique platform for the systematic investigation of the factors governing the pairing of antibody heavy and light chains. By examining a range of characteristics, including amino acid conservation, structural features, charge distribution, and interface residue identity, we challenge the prevailing assumption that pairing is random. Our findings indicate that specific physicochemical properties of single amino acid residues may influence the compatibility and affinity of heavy and light chain combinations. Further structural analyses based on antibody Fv fragments deposited in the Protein Data Bank (PDB) provide insights into the underlying structural features driving these pairing preferences, including a novel definition for the residues constituting the VH-VL interface, based on a collection of over 3500 structures. These results have significant implications for understanding antibody assembly and may guide the rational design of therapeutic antibodies with desired properties. Moreover, we provide a complete description and reference characterizing the various human germlines. |
| format | Article |
| id | doaj-art-0162f6377d3b4bc8ae12b19e74f8e7c7 |
| institution | OA Journals |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-0162f6377d3b4bc8ae12b19e74f8e7c72025-08-20T02:34:09ZengTaylor & Francis GroupmAbs1942-08621942-08702025-12-0117110.1080/19420862.2025.2507950Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural featuresClarissa A. Seidler0Vera A. Spanke1Jakob Gamper2Alexander Bujotzek3Guy Georges4Klaus R. Liedl5Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, AustriaDepartment of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, AustriaDepartment of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, AustriaRoche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Penzberg, GermanyRoche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Penzberg, GermanyDepartment of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, AustriaThe Observed Antibody Space provides the most abundant collection of annotated paired antibody variable domain sequences, thus offering a unique platform for the systematic investigation of the factors governing the pairing of antibody heavy and light chains. By examining a range of characteristics, including amino acid conservation, structural features, charge distribution, and interface residue identity, we challenge the prevailing assumption that pairing is random. Our findings indicate that specific physicochemical properties of single amino acid residues may influence the compatibility and affinity of heavy and light chain combinations. Further structural analyses based on antibody Fv fragments deposited in the Protein Data Bank (PDB) provide insights into the underlying structural features driving these pairing preferences, including a novel definition for the residues constituting the VH-VL interface, based on a collection of over 3500 structures. These results have significant implications for understanding antibody assembly and may guide the rational design of therapeutic antibodies with desired properties. Moreover, we provide a complete description and reference characterizing the various human germlines.https://www.tandfonline.com/doi/10.1080/19420862.2025.2507950Antibody pairinggermline V-geneVH-VL interfaceantibody assemblydatabase analysis |
| spellingShingle | Clarissa A. Seidler Vera A. Spanke Jakob Gamper Alexander Bujotzek Guy Georges Klaus R. Liedl Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features mAbs Antibody pairing germline V-gene VH-VL interface antibody assembly database analysis |
| title | Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features |
| title_full | Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features |
| title_fullStr | Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features |
| title_full_unstemmed | Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features |
| title_short | Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features |
| title_sort | data driven analyses of human antibody variable domain germlines pairings sequences and structural features |
| topic | Antibody pairing germline V-gene VH-VL interface antibody assembly database analysis |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2025.2507950 |
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