Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines
Antibodies and other new antibody-like formats have emerged as one of the most rapidly growing classes of biotherapeutic proteins. Understanding the structural features that drive antibody function and, consequently, their molecular recognition is critical for engineering antibodies. Here, we presen...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Antibodies |
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| Online Access: | https://www.mdpi.com/2073-4468/12/4/67 |
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| author | Monica L. Fernández-Quintero Nancy D. Pomarici Anna-Lena M. Fischer Valentin J. Hoerschinger Katharina B. Kroell Jakob R. Riccabona Anna S. Kamenik Johannes R. Loeffler James A. Ferguson Hailee R. Perrett Klaus R. Liedl Julianna Han Andrew B. Ward |
| author_facet | Monica L. Fernández-Quintero Nancy D. Pomarici Anna-Lena M. Fischer Valentin J. Hoerschinger Katharina B. Kroell Jakob R. Riccabona Anna S. Kamenik Johannes R. Loeffler James A. Ferguson Hailee R. Perrett Klaus R. Liedl Julianna Han Andrew B. Ward |
| author_sort | Monica L. Fernández-Quintero |
| collection | DOAJ |
| description | Antibodies and other new antibody-like formats have emerged as one of the most rapidly growing classes of biotherapeutic proteins. Understanding the structural features that drive antibody function and, consequently, their molecular recognition is critical for engineering antibodies. Here, we present the structural architecture of conventional IgG antibodies alongside other formats. We emphasize the importance of considering antibodies as conformational ensembles in solution instead of focusing on single-static structures because their functions and properties are strongly governed by their dynamic nature. Thus, in this review, we provide an overview of the unique structural and dynamic characteristics of antibodies with respect to their antigen recognition, biophysical properties, and effector functions. We highlight the numerous technical advances in antibody structure prediction and design, enabled by the vast number of experimentally determined high-quality structures recorded with cryo-EM, NMR, and X-ray crystallography. Lastly, we assess antibody and vaccine design strategies in the context of structure and dynamics. |
| first_indexed | 2024-03-08T21:03:04Z |
| format | Article |
| id | doaj.art-ebfea549dcaf49caafa4ea894542b32c |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-08T21:03:04Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-ebfea549dcaf49caafa4ea894542b32c2023-12-22T13:48:09ZengMDPI AGAntibodies2073-44682023-10-011246710.3390/antib12040067Structure and Dynamics Guiding Design of Antibody Therapeutics and VaccinesMonica L. Fernández-Quintero0Nancy D. Pomarici1Anna-Lena M. Fischer2Valentin J. Hoerschinger3Katharina B. Kroell4Jakob R. Riccabona5Anna S. Kamenik6Johannes R. Loeffler7James A. Ferguson8Hailee R. Perrett9Klaus R. Liedl10Julianna Han11Andrew B. Ward12Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USAInstitute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, AustriaDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USAAntibodies and other new antibody-like formats have emerged as one of the most rapidly growing classes of biotherapeutic proteins. Understanding the structural features that drive antibody function and, consequently, their molecular recognition is critical for engineering antibodies. Here, we present the structural architecture of conventional IgG antibodies alongside other formats. We emphasize the importance of considering antibodies as conformational ensembles in solution instead of focusing on single-static structures because their functions and properties are strongly governed by their dynamic nature. Thus, in this review, we provide an overview of the unique structural and dynamic characteristics of antibodies with respect to their antigen recognition, biophysical properties, and effector functions. We highlight the numerous technical advances in antibody structure prediction and design, enabled by the vast number of experimentally determined high-quality structures recorded with cryo-EM, NMR, and X-ray crystallography. Lastly, we assess antibody and vaccine design strategies in the context of structure and dynamics.https://www.mdpi.com/2073-4468/12/4/67antibodystructure predictionantibody structure determinationmolecular dynamicsX-ray crystallographyNMR |
| spellingShingle | Monica L. Fernández-Quintero Nancy D. Pomarici Anna-Lena M. Fischer Valentin J. Hoerschinger Katharina B. Kroell Jakob R. Riccabona Anna S. Kamenik Johannes R. Loeffler James A. Ferguson Hailee R. Perrett Klaus R. Liedl Julianna Han Andrew B. Ward Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines Antibodies antibody structure prediction antibody structure determination molecular dynamics X-ray crystallography NMR |
| title | Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines |
| title_full | Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines |
| title_fullStr | Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines |
| title_full_unstemmed | Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines |
| title_short | Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines |
| title_sort | structure and dynamics guiding design of antibody therapeutics and vaccines |
| topic | antibody structure prediction antibody structure determination molecular dynamics X-ray crystallography NMR |
| url | https://www.mdpi.com/2073-4468/12/4/67 |
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