Szalai A J, Agrawal A, Greenhough T J, Volanakis J E
Department of Medicine, University of Alabama at Birmingham, 35294-0006, USA.
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.
人C反应蛋白是一种结合钙离子的急性期蛋白，对磷酸胆碱具有结合特异性。最近的晶体学和诱变研究为该蛋白的结构生物学提供了坚实的理解，而使用转基因小鼠的实验证实了其宿主防御功能。该蛋白由五个呈环状对称的相同亚基组成。在每个亚基的一个面上，有一个磷酸胆碱结合位点，由两个连接磷酸基团的钙离子和一个容纳磷酸胆碱甲基的疏水口袋组成。在相对的面上，是一个由N端和C端部分形成的深裂缝，由一个α-螺旋界定。突变研究表明，该分子的C1q结合位点位于这个裂缝的开口端，天冬氨酸112和酪氨酸175代表接触残基。我们使用人C反应蛋白转基因小鼠研究了该蛋白的宿主防御功能。与野生型小鼠相比，感染肺炎链球菌的转基因小鼠寿命延长，死亡率降低。这归因于主要由C反应蛋白与补体相互作用介导的菌血症减少了多达400倍。还证明了一种不依赖补体的宿主保护作用。
