Tom-Yew Stacey A L, Cui Diana T, Bekker Elena G, Murphy Michael E P
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
J Biol Chem. 2005 Mar 11;280(10):9283-90. doi: 10.1074/jbc.M412479200. Epub 2004 Dec 21.
Campylobacter jejuni, the leading cause of human gastroenteritis, expresses a ferric binding protein (cFbpA) that in many pathogenic bacteria functions to acquire iron as part of their virulence repertoire. Recombinant cFbpA is isolated with ferric iron bound from Escherichia coli. The crystal structure of cFbpA reveals unprecedented iron coordination by only five protein ligands. The histidine and one tyrosine are derived from the N-terminal domain, whereas the three remaining tyrosine ligands are from the C-terminal domain. Surprisingly, a synergistic anion present in all other characterized ferric transport proteins is not observed in the cFbpA iron-binding site, suggesting a novel role for this protein in iron uptake. Furthermore, cFbpA is shown to bind iron with high affinity similar to Neisserial FbpA and exhibits an unusual preference for ferrous iron (oxidized subsequently to the ferric form) or ferric iron chelated by oxalate. Sequence and structure analyses reveal that cFbpA is a member of a new class of ferric binding proteins that includes homologs from invasive and intracellular bacteria as well as cyanobacteria. Overall, six classes are defined based on clustering within the tree and by their putative iron coordination. The absence of a synergistic anion in the iron coordination sphere of cFbpA also suggests an alternative model of evolution for FbpA homologs involving an early iron-binding ancestor instead of a requirement for a preexisting anion-binding ancestor.
空肠弯曲菌是人类肠胃炎的主要病因，它表达一种铁结合蛋白（cFbpA），在许多致病细菌中，这种蛋白作为其毒力组成部分发挥获取铁的作用。重组cFbpA是从结合了三价铁的大肠杆菌中分离出来的。cFbpA的晶体结构显示，仅由五个蛋白质配体就实现了前所未有的铁配位。组氨酸和一个酪氨酸来自N端结构域，而其余三个酪氨酸配体来自C端结构域。令人惊讶的是，在cFbpA的铁结合位点未观察到所有其他已表征的铁转运蛋白中都存在的协同阴离子，这表明该蛋白在铁摄取中具有新的作用。此外，cFbpA被证明与奈瑟氏菌FbpA一样，以高亲和力结合铁，并且对亚铁（随后氧化为三价铁形式）或被草酸盐螯合的三价铁表现出不同寻常的偏好。序列和结构分析表明，cFbpA是一类新的铁结合蛋白的成员，这类蛋白包括来自侵袭性和细胞内细菌以及蓝细菌的同源物。总体而言，根据在系统树中的聚类及其假定的铁配位定义了六个类别。cFbpA的铁配位球中不存在协同阴离子，这也暗示了FbpA同源物的一种替代进化模型，即涉及一个早期的铁结合祖先，而不是需要一个预先存在的阴离子结合祖先。
