title: C-reactive protein: structural biology and host defense function.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294-0006, USA. rheu022@uabdpo.dpo.uab.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Szalai
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
authors.forename: T J
authors.initials: TJ
authors.lastname: Greenhough
authors.forename: J E
authors.initials: JE
authors.lastname: Volanakis
mesh_terms: D000818:Animals; D001665:Binding Sites; D002097:C-Reactive Protein / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008024:Ligands; D011487:Protein Conformation
chemical_list: D008024:Ligands; D003165:Complement System Proteins; D002097:C-Reactive Protein