Ferric iron reductases and their contribution to unicellular ferrous iron uptake.

Ferric iron reductases and their contribution to unicellular ferrous iron uptake.
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DOI:
10.1016/j.jinorgbio.2021.111407
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发表时间:
2021-05
影响因子:
3.9
通讯作者:
Smith AT
Smith AT
中科院分区:
生物学2区
文献类型:
--
作者:
Cain TJ;Smith AT

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铁是几乎所有生命形式的必需元素,并且获得这种微量营养素的能力已被确定为单细胞病原体建立感染的关键毒力因子。在O2存在下,铁通常以三价铁(Fe 3+)氧化态存在,其在水性条件下高度不稳定,需要将其螯合到辅因子和/或宿主蛋白中以保持可溶性。为了对抗这种不溶性,并与宿主螯合机制竞争,许多单细胞病原体将分泌低分子量,高亲和力的Fe 3+螯合剂,称为铁载体。一旦获得,单细胞病原体必须释放铁载体结合的Fe 3+,以便将这种营养素吸收到代谢途径中。虽然这些生物体可以水解铁载体骨架以释放螯合的Fe 3+,但这种方法在能量上是昂贵的。相反,铁可以通过还原为Fe 2+从Fe 3 + -铁载体复合物中释放出来,这产生了高度可溶的低亲和力形式的铁。这种还原是由一类称为铁还原酶的酶进行的。铁还原酶是广泛分布的电子传递蛋白,由许多感染性生物表达,并与单细胞病原体的毒力有关。尽管如此重要,铁还原酶仍然知之甚少。本文综述了我们目前对单细胞铁还原酶(可溶性和膜结合的)的认识,强调了铁还原酶介导的Fe 3+还原和通过亚铁转运蛋白转运Fe 2+之间重要但未被充分认识的联系。铁的获得对于单细胞生物体的生存至关重要,特别是在发病过程中。许多感染性生物体使用铁还原酶从Fe 3+络合物(包括铁载体和宿主蛋白质)中释放Fe 2+。因此,铁还原酶的使用将三价铁和二价铁的运输联系起来。
Iron is a necessary element for nearly all forms of life, and the ability to acquire this trace nutrient has been identified as a key virulence factor for the establishment of infection by unicellular pathogens. In the presence of O2, iron typically exists in the ferric (Fe3+) oxidation state, which is highly unstable in aqueous conditions, necessitating its sequestration into cofactors and/or host proteins to remain soluble. To counter this insolubility, and to compete with host sequestration mechanisms, many unicellular pathogens will secrete low molecular weight, high-affinity Fe3+ chelators known as siderophores. Once acquired, unicellular pathogens must liberate the siderophore-bound Fe3+ in order to assimilate this nutrient into metabolic pathways. While these organisms may hydrolyze the siderophore backbone to release the chelated Fe3+, this approach is energetically costly. Instead, iron may be liberated from the Fe3+ - siderophore complex through reduction to Fe2+, which produces a lower-affinity form of iron that is highly soluble. This reduction is performed by a class of enzymes known as ferric reductases. Ferric reductases are broadly-distributed electron-transport proteins that are expressed by numerous infectious organisms and are connected to the virulence of unicellular pathogens. Despite this importance, ferric reductases remain poorly understood. This review provides an overview of our current understanding of unicellular ferric reductases (both soluble and membrane-bound), with an emphasis on the important but underappreciated connection between ferric-reductase mediated Fe3+ reduction and the transport of Fe2+ via ferrous iron transporters. Iron acquisition is crucial for the survival of unicellular organisms, particularly during pathogenesis. Many infectious organisms use ferric reductase enzymes to liberate Fe2+ from Fe3+ complexes, including siderophores and host proteins. The use of ferric reductases thus links ferric and ferrous iron transport.
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