Human calprotectin is an iron-sequestering host-defense protein.
Human calprotectin is an iron-sequestering host-defense protein.
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DOI：
10.1038/nchembio.1891
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发表时间：
2015-10
影响因子：
14.8
通讯作者：
Nolan EM
中科院分区：
文献类型：
--
作者：
Nakashige TG;Zhang B;Krebs C;Nolan EM
人钙保护素(CP)是一种金属螯合的天然免疫反应的抗微生物蛋白。目前的工作模型指出，CP将锰和锌从病原体中隔离出来。我们报告了一项发现，CP螯合铁并剥夺细菌这种必要的营养。对经CP处理的生长介质进行的元素分析表明，CP降低了锰、铁和锌的浓度。微生物生长研究表明，CP对铁的耗竭有助于抑制细菌病原体的生长。生化研究表明，CP与Fe(II)配位在一个不寻常的六组氨酸基序上，57Fe(II)结合CP的穆斯堡尔谱与该位置高自旋Fe(II)的配位一致(δ=1.2 mm/S，ΔEQ=1.78 mm/S)。在Ca(II)存在的情况下，CP开启了它的铁隔离功能，并对Fe(II)表现出亚皮摩尔亲和力。我们的发现扩展了铁的生物配位化学，并支持CP在哺乳动物铁稳态中以前未被认识到的作用。
Human calprotectin (CP) is a metal-chelating antimicrobial protein of the innate immune response. The current working model states that CP sequesters manganese and zinc from pathogens. We report the discovery that CP chelates iron and deprives bacteria of this essential nutrient. Elemental analysis of CP-treated growth medium establishes that CP reduces the concentrations of manganese, iron, and zinc. Microbial growth studies reveal that iron depletion by CP contributes to the growth inhibition of bacterial pathogens. Biochemical investigations demonstrate that CP coordinates Fe(II) at an unusual hexahistidine motif, and the Mössbauer spectrum of 57Fe(II)-bound CP is consistent with coordination of high-spin Fe(II) at this site (δ = 1.20 mm/s, ΔEQ = 1.78 mm/s). In the presence of Ca(II), CP turns on its iron-sequestering function and exhibits sub-picomolar affinity for Fe(II). Our findings expand the biological coordination chemistry of iron and support a previously unappreciated role for CP in mammalian iron homeostasis.