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Alexander J. Szalai, Alok Agrawal, Trevor J. Greenhough, John E. Volanakis

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 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 ?-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.

Clinical Chemical Laboratory Medicine, Walter de Gruyter

Print ISSN: 1434-6621
Volume: 37, 03/1999
Pages: 265 - 270

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