Kinetics of heme transfer by the Shr NEAT domains of Group A Streptococcus.
Kinetics of heme transfer by the Shr NEAT domains of Group A Streptococcus.
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DOI：
10.1016/j.abb.2013.08.009
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发表时间：
2013-10
影响因子：
3.9
通讯作者：
Mahamoudou Ouattara;A. Pennati;Darius J. Devlin;Ya-Shu Huang;G. Gadda;Z. Eichenbaum
中科院分区：
文献类型：
--
作者：
Mahamoudou Ouattara;A. Pennati;Darius J. Devlin;Ya-Shu Huang;G. Gadda;Z. Eichenbaum
溶血 A 族链球菌 (GAS) 是一种臭名昭著的人类病原体。 GAS 的 Shr 蛋白通过从宿主血红蛋白中获取血红素并将其递送至表面相邻的受体 Shp 来参与铁的获取。然后血红素被输送到 SiaABC 蛋白进行跨膜运输。通过快速动力学研究，我们研究了 Shr 的两个血红素结合 NEAT 模块的作用。停流分析表明，holoNEAT1 快速将血红素递送至 apoShp。 HoloNEAT2 没有表现出这样的活性；仅观察到血红素从 NEAT2 到 apoShp 的转移很少且缓慢，这表明 Shr NEAT 结构域在血红素运输中具有独特的作用。 HoloNEAT1 还通过快速且可逆的过程向 apoNEAT2 提供血红素。据我们所知，这是在同一受体的分离的 NEAT 结构域之间观察到的首次转移。序列比对显示，Shr NEAT 结构域属于 NEAT 结构域的两个家族，这两个家族在多个物种的 Shr 直向同源物中是保守的。基于血红素转移动力学，我们提出 Shr 蛋白根据血红素可用性调节血红素摄取，其机制是 NEAT1 促进血红素快速递送至 Shp，而 NEAT2 充当细菌表面血红素的临时储存。
The hemolytic Group A Streptococcus (GAS) is a notorious human pathogen. Shr protein of GAS participates in iron acquisition by obtaining heme from host hemoglobin and delivering it to the adjacent receptor on the surface, Shp. Heme is then conveyed to the SiaABC proteins for transport across the membrane. Using rapid kinetic studies, we investigated the role of the two heme binding NEAT modules of Shr. Stopped-flow analysis showed that holoNEAT1 quickly delivered heme to apoShp. HoloNEAT2 did not exhibit such activity; only little and slow transfer of heme from NEAT2 to apoShp was seen, suggesting that Shr NEAT domains have distinctive roles in heme transport. HoloNEAT1 also provided heme to apoNEAT2, by a fast and reversible process. To the best of our knowledge this is the first transfer observed between isolated NEAT domains of the same receptor. Sequence alignment revealed that Shr NEAT domains belong to two families of NEAT domains that are conserved in Shr orthologs from several species. Based on the heme transfer kinetics, we propose that Shr proteins modulate heme uptake according to heme availability by a mechanism where NEAT1 facilitates fast heme delivery to Shp, whereas NEAT2 serves as a temporary storage for heme on the bacterial surface.