C-reactive protein: Structural biology and host defense function

Human C-reactive protein is a Ca2+-binding acute phase-protein with binding specificity for phosphocholine. Recent crystallographic and mutagenesis st udies have provided a solid understanding of the structural biology of the protein, while experiments using transgenic mice have confirmed its host-de fense function. The protein consists of five identical protomers in cyclic symmetry. On one face of each protomer there is a binding site for phosphoc holine consisting of two Ca2+ ions that ligate the phosphate group and a hy drophobic pocket that accommodates the methyl groups of phosphocholine. On the opposite face is a deep cleft formed by parts of the hi and C termini a nd bordered by an or-helix. Mutational studies indicate that the C1q-bindin g site of the molecule is located at the open end of this cleft with Asp(11 2) and Tyr(175) representing contact residues. Using human C-reactive prote in transgenic mice, we investigated the host defense functions of the prote in. Transgenic mice infected with Streptococcus pneumoniae had increased li fespan and lowered mortality compared to wild-type mice. This was attributa ble to an up to 400-fold reduction in bacteremia mediated mainly by the int eraction of C-reactive protein with complement. A complement-independent ho st protective effect was also demonstrated.