Sebulsky M Tom, Speziali Craig D, Shilton Brian H, Edgell David R, Heinrichs David E
Department of Microbiology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
J Biol Chem. 2004 Dec 17;279(51):53152-9. doi: 10.1074/jbc.M409793200. Epub 2004 Oct 8.
Staphylococcus aureus can utilize ferric hydroxamates as a source of iron under iron-restricted growth conditions. Proteins involved in this transport process are: FhuCBG, which encodes a traffic ATPase; FhuD2, a post-translationally modified lipoprotein that acts as a high affinity receptor at the cytoplasmic membrane for the efficient capture of ferric hydroxamates; and FhuD1, a protein with similarity to FhuD2. Gene duplication likely gave rise to fhuD1 and fhuD2. While the genomic locations of fhuCBG and fhuD2 in S. aureus strains are conserved, both the presence and the location of fhuD1 are variable. The apparent redundancy of FhuD1 led us to examine the role of this protein. We demonstrate that FhuD1 is expressed only under conditions of iron limitation through the regulatory activity of Fur. FhuD1 fractions with the cell membrane and binds hydroxamate siderophores but with lower affinity than FhuD2. Using small angle x-ray scattering, the solution structure of FhuD1 resembles that of FhuD2, and only a small conformational change is associated with ferrichrome binding. FhuD1, therefore, appears to be a receptor for ferric hydroxamates, like FhuD2. Our data to date suggest, however, that FhuD1 is redundant to FhuD2 and plays a minor role in hydroxamate transport. However, given the very real possibility that we have not yet identified the proper conditions where FhuD1 does provide an advantage over FhuD2, we anticipate that FhuD1 serves an enhanced role in the transport of untested hydroxamate siderophores and that it may play a prominent role during the growth of S. aureus in its natural environments.
在铁限制生长条件下，金黄色葡萄球菌可以利用高铁异羟肟酸盐作为铁源。参与这一转运过程的蛋白质有：FhuCBG，编码一种转运ATP酶；FhuD2，一种翻译后修饰的脂蛋白，在细胞质膜上作为高亲和力受体，用于高效捕获高铁异羟肟酸盐；以及FhuD1，一种与FhuD2相似的蛋白质。基因复制可能产生了fhuD1和fhuD2。虽然金黄色葡萄球菌菌株中fhuCBG和fhuD2的基因组位置是保守的，但fhuD1的存在和位置都是可变的。FhuD1明显的冗余性促使我们研究这种蛋白质的作用。我们证明，FhuD1仅在铁限制条件下通过Fur的调节活性表达。FhuD1与细胞膜结合并结合异羟肟酸铁载体，但亲和力低于FhuD2。使用小角X射线散射，FhuD1的溶液结构与FhuD2相似，并且只有一个小的构象变化与高铁色素结合相关。因此，FhuD1似乎是高铁异羟肟酸盐的受体，就像FhuD2一样。然而，我们目前的数据表明，FhuD1相对于FhuD2是冗余的，并且在异羟肟酸盐转运中起次要作用。然而，鉴于我们尚未确定FhuD1确实比FhuD2具有优势的合适条件这一非常现实的可能性，我们预计FhuD1在未测试的异羟肟酸铁载体的转运中发挥增强作用，并且它可能在金黄色葡萄球菌在其自然环境中的生长过程中发挥重要作用。
