Structures of CRP antigen-antibody complexes provide insights into the mechanism of specific recognition
Antigen-antibody specific recognition constitutes fundamental research in molecular drug design and immune diagnostics, where cumulative non-covalent interactions critically determine binding affinities. Current mechanistic understanding of antibody affinity optimization remains incomplete, hindering rational structure-based design of therapeutic antibodies and bispecific variants. This study presents four cryo-EM structures of C-reactive protein (CRP) complexed with heavy-chain antibodies (HCAbs) of varying affinities, resolved at 3.0-3.4 Å resolution. Comparative structural analysis reveals pronounced variations in binding modalities among affinity-differentiated HCAbs, while identifying critical determinants of engagement conformations, providing mechanistic insights for rational optimization of CRP-specific antibodies.
Authors
- Yijian Li (ORCID: https://orcid.org/0000-0003-1416-4535)
- Tonggong Liu
- Dayong Gu (ORCID: https://orcid.org/0000-0002-9547-8474)
- Jingzhe Wang (ORCID: https://orcid.org/0000-0001-8332-7997)
- Wei Qiu (ORCID: https://orcid.org/0000-0003-0600-1306)
- Yong Peng (ORCID: https://orcid.org/0000-0003-3377-6131)
- Fuxing Zeng (ORCID: https://orcid.org/0000-0003-0790-0151)
- Jian Zhang (ORCID: https://orcid.org/0000-0002-6558-791X)
- Chaohui Duan (ORCID: https://orcid.org/0000-0003-3130-5045)
- Qianxi Yu (ORCID: https://orcid.org/0009-0007-9972-9860)
- Mengtan Du
Institutions
- Sun Yat-sen University (CN)
- Southern University of Science and Technology (CN)
- AbMax AntibodyChina (China) (CN)
- Sun Yat-sen Memorial Hospital (CN)
- ShenZhen People’s Hospital (CN)
- Shenzhen Bao'an District People's Hospital (CN)
- Guangdong Provincial Center for Disease Control and Prevention (CN)
- Shenzhen Second People's Hospital (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1038/s42003-025-08941-9
- Citations
- 1
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 1.36
Funders
- National Natural Science Foundation of China
- Shenzhen University
- Southern University of Science and Technology
- National Key Research and Development Program of China
- Science and Technology Planning Project of Guangdong Province
- Division of Graduate Education