Moraes Trevor F, Yu Rong-hua, Strynadka Natalie C J, Schryvers Anthony B
Department of Biochemistry and Molecular Biology, Center for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Mol Cell. 2009 Aug 28;35(4):523-33. doi: 10.1016/j.molcel.2009.06.029.
Pathogenic bacteria from the Neisseriaceae and Pasteurellacea families acquire iron directly from the host iron-binding glycoprotein, transferrin (Tf), in a process mediated by surface receptor proteins that directly bind host Tf, extract the iron, and transport it across the outer membrane. The bacterial Tf receptor is comprised of a surface exposed lipoprotein, Tf-binding protein B (TbpB), and an integral outer-membrane protein, Tf-binding protein A (TbpA), both of which are essential for survival in the host. In this study, we report the 1.98 A resolution structure of TbpB from the porcine pathogen Actinobacillus pleuropneumoniae, providing insights into the mechanism of Tf binding and the role of TbpB. A model for the complex of TbpB bound to Tf is proposed. Mutation of a single surface-exposed Phe residue on TbpB within the predicted interface completely abolishes binding to Tf, suggesting that the TbpB N lobe comprises the sole high-affinity binding region for Tf.
奈瑟菌科和巴斯德菌科的致病细菌通过表面受体蛋白介导的过程直接从宿主铁结合糖蛋白转铁蛋白（Tf）获取铁。这些表面受体蛋白直接结合宿主Tf，提取铁并将其转运穿过外膜。细菌Tf受体由表面暴露的脂蛋白转铁蛋白结合蛋白B（TbpB）和外膜整合蛋白转铁蛋白结合蛋白A（TbpA）组成，二者对于在宿主体内存活均至关重要。在本研究中，我们报道了猪胸膜肺炎放线杆菌TbpB的分辨率为1.98 Å的结构，这为深入了解Tf结合机制以及TbpB的作用提供了线索。我们提出了TbpB与Tf结合复合物的模型。预测界面内TbpB上单个表面暴露的苯丙氨酸残基发生突变会完全消除与Tf的结合，这表明TbpB的N叶包含Tf的唯一高亲和力结合区域。
