HutZ is required for efficient heme utilization in Vibrio cholerae

HutZ is required for efficient heme utilization in Vibrio cholerae
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DOI:
10.1128/jb.186.13.4142-4151.2004
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发表时间:
2004-07-01
影响因子:
3.2
通讯作者:
Payne, SM
Payne, SM
中科院分区:
生物学3区
文献类型:
--
作者:
Wyckoff, EE;Schmitt, M;Payne, SM

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霍乱弧菌,霍乱的病原体,需要铁的增长。它获得铁的一种机制是血红素的摄取,并且已经在霍乱弧菌中鉴定了几个血红素利用基因。这些包括三种不同的外膜受体、两个TonB系统和一个明显的ABC转运蛋白,用于将血红素转移穿过内膜。然而,人们对血红素进入细胞后的命运知之甚少。在这份报告中,我们表明,一种新的血红素利用蛋白,HutZ,需要最佳的血红素利用。hutZ(开放阅读框[ORF] VCA 0907)与另外两个基因hutW(ORF VCA 0909)和hutX(ORF VCA 0908)一起编码,在从tonB 1操纵子分化转录的操纵子中。当提供血红素作为唯一的铁源时,hutZ突变体生长不良,并且生长不良可能是由于未能有效地利用血红素作为铁源,而不是血红素毒性。白喉棒状杆菌和C.溃疡患者不能使用血红素作为铁源。当hutWXZ基因在血红素加氧酶突变体中表达时,血红素上的生长得以恢复,而hutZ是这种效应所必需的。生化特性表明,HutZ结合血红素具有高效率,但是,没有血红素加氧酶活性检测到这种蛋白质。HutZ可以作为血红素储存蛋白,也可以作为穿梭蛋白,增加血红素从膜运输到含血红素蛋白的效率。
Vibrio cholerae, the causative agent of cholera, requires iron for growth. One mechanism by which it acquires iron is the uptake of heme, and several heme utilization genes have been identified in V. cholerae. These include three distinct outer membrane receptors, two TonB systems, and an apparent ABC transporter to transfer heme across the inner membrane. However, little is known about the fate of the heme after it enters the cell. In this report we show that a novel heme utilization protein, HutZ, is required for optimal heme utilization. hutZ (open reading frame [ORF] VCA0907) is encoded with two other genes, hutW (ORF VCA0909) and hutX (ORF VCA0908), in an operon divergently transcribed from the tonB1 operon. A hutZ mutant grew poorly when heme was provided as the sole source of iron, and the poor growth was likely due to the failure to use heme efficiently as a source of iron, rather than to heme toxicity. Heme oxygenase mutants of both Corynebacterium diphtheriae and C. ulcerans fail to use heme as an iron source. When the hutWXZ genes were expressed in the heme oxygenase mutants, growth on heme was restored, and hutZ was required for this effect. Biochemical characterization indicated that HutZ binds heme with high efficiency; however, no heme oxygenase activity was detected for this protein. HutZ may act as a heme storage protein, and it may also function as a shuttle protein that increases the efficiency of heme trafficking from the membrane to heme-containing proteins.