C-reactive protein: structure, function, regulation, and role in clinical diseases

Abstract

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.

Keywords: C-reactive protein; acute phase; inflammation; pentamer; structure.

Figure 1

The native structure and associated activities of CRP are evolutionarily conserved. (A) Cryo-EM structure of CRP complexes with PC. The CRP-PC complex was achieved from Protein Data Bank (PDB entry 7PKE) and the ribbon diagram of the CRP Cryo-EM structure of CRP-PC-Ca²⁺ was generated by ChimeraX software (27). (B) View of the ligand binding face of mCRP. Each protomer contains a binding site, which is shown occupied by 2 calcium (green) and 1 PC molecule (magenta). (C) Side view of the pentameric form of CRP. Which mediates PC ligand-binding named recognition face, and the other side possesses a single α-helix, which binds to ligands such as C1q, therefore named effector face. (D) The pentameric form structures of mouse and rat CRP were generated with AlphaFold 3 using five subunits (28).