Structures of CRP antigen-antibody complexes provide insights into the mechanism of specific recognition

作者：Yijian Li, Qianxi Yu, Mengtan Du, Jian Zhang, Tonggong Liu, Jingzhe Wang, Qingchun Wei, Yong Peng, Chaohui Duan, Dayong Gu, Fuxing Zeng · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-08941-9 · 被引用次数：2 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Advanced Biosensing Techniques and Applications、Animal health and immunology

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. Structural differences in CRP antigen-antibody engagement conformations elucidate distinct binding modalities, providing mechanistic insights for the rational optimization of CRP-specific antibodies.