C-reactive protein: structural biology and host defense function

Clin Chem Lab Med. 1999 Mar;37(3):265-70. doi: 10.1515/CCLM.1999.046.


Human C-reactive protein is a Ca2+-binding acute phase-protein with binding specificity for phosphocholine. Recent crystallographic and mutagenesis studies have provided a solid understanding of the structural biology of the protein, while experiments using transgenic mice have confirmed its host-defense function. The protein consists of five identical protomers in cyclic symmetry. On one face of each protomer there is a binding site for phosphocholine consisting of two Ca2+ ions that ligate the phosphate group and a hydrophobic pocket that accommodates the methyl groups of phosphocholine. On the opposite face is a deep cleft formed by parts of the N and C termini and bordered by an alpha-helix. Mutational studies indicate that the C1q-binding site of the molecule is located at the open end of this cleft with Asp112 and Tyr175 representing contact residues. Using human C-reactive protein transgenic mice, we investigated the host defense functions of the protein. Transgenic mice infected with Streptococcus pneumoniae had increased lifespan and lowered mortality compared to wild-type mice. This was attributable to an up to 400-fold reduction in bacteremia mediated mainly by the interaction of C-reactive protein with complement. A complement-independent host protective effect was also demonstrated.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • C-Reactive Protein / chemistry*
  • C-Reactive Protein / immunology*
  • C-Reactive Protein / metabolism
  • Complement System Proteins / metabolism
  • Complement System Proteins / physiology
  • Humans
  • Ligands
  • Protein Conformation


  • Ligands
  • Complement System Proteins
  • C-Reactive Protein