Cryo‐ <scp>EM</scp> structure of pentameric C‐reactive protein in complex with monoclonal <scp>IgG</scp> antibodies

C-reactive protein (CRP) plays a central role in innate immunity and serves as a key biomarker of inflammation. Despite its clinical importance, the structural basis of CRP interactions with antibodies remains poorly characterized. Using cryo-electron microscopy (cryo-EM), we resolved the structure of immune complexes formed between pentameric CRP and monoclonal immunoglobulin G (IgG) antibodies at up to 2.4 Å resolution. The complexes display a barrel-shaped architecture, with two CRP pentamers bridged by three to five antibodies. We built an atomic model of the CRP-antibody interface, identifying a binding site on the A-face of CRP mediated exclusively by hydrogen bonds, without salt-bridge formation. These findings provide structural insights into CRP-IgG recognition and offer a basis for the rational design of improved antibodies.