The crystal structure of the secreted dimeric form of the hemophore HasA reveals a domain swapping with an exchanged heme ligand
The crystal structure of the secreted dimeric form of the hemophore HasA reveals a domain swapping with an exchanged heme ligand
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DOI：
10.1016/j.jmb.2006.10.063
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发表时间：
2007-01-26
影响因子：
5.6
通讯作者：
Izadi-Pruneyre, Nadia
中科院分区：
文献类型：
--
作者：
Czjzek, Mirjam;Letoffe, Sylvie;Izadi-Pruneyre, Nadia
为了满足它们的铁需求，一些革兰氏阴性细菌使用血红素摄取系统，该系统涉及称为血细胞的细胞外血红素结合蛋白。血细胞的功能是获得游离或与血红素蛋白结合的血红素，并通过蛋白质-蛋白质相互作用将其转移到其特异性外膜受体HasR。粘质沙雷氏菌分泌的血细胞HasA是一种机会致病菌，是第一个被鉴定出来的，现在已经得到了很好的鉴定。HasA是以强亲和力结合一个B血红素的单体。HasA中的血红素高度暴露于溶剂中，并与一对不寻常的配体组氨酸和酪氨酸配位。marcescens：DHasA.我们发现，无论是单体和二聚体形式分泌缺铁条件下的S。marcescens。DHasA的晶体结构表明它是一个结构域交换的二聚体。DHasA的每个单体亚基的整体结构与HasA非常相似，但由来自两条不同多肽链的部分con-Ling形成，涉及其中一个血红素配体。因此，DHasA通过来自两条多肽链的残基结合两个血红素分子。我们在这里表明，虽然DHasA可以结合两个血红素分子，但它不能将它们传递给受体HasR。然而，DHasA可以有效地将其血红素转化为单体形式，进而将其传递给HasR。我们假设，DHasA可以作为血红素水库的血细胞系统。(c)2006爱思唯尔有限公司保留所有权利。
To satisfy their iron needs, several Gram-negative bacteria use a heme uptake system involving an extracellular heme-binding protein called hemophore. The function of the hemophore is to acquire free or hemoprotein-bound heme and to transfer it to HasR, its specific outer membrane receptor, by protein-protein interaction. The hemophore HasA secreted by Serratia marcescens, an opportunistic pathogen, was the first to be identified and is now very well characterized. HasA is a monomer that binds one b heme with strong affinity. The heme in HasA is highly exposed to solvent and coordinated by an unusual pair of ligands, a histidine and a tyrosine.Here, we report the identification, the characterization and the X-ray structure of a dimeric form of HasA from S. marcescens: DHasA. We show that both monomeric and dimeric forms are secreted in iron deficient conditions by S. marcescens. The crystal structure of DHasA reveals that it is a domain swapped dimer. The overall structure of each monomeric subunit of DHasA is very similar to that of HasA but formed by parts con-Ling from the two different polypeptide chains, involving one of the heme ligands. Consequently DHasA binds two heme molecules by residues coming from both polypeptide chains. We show here that, while DHasA can bind two heme molecules, it is not able to deliver them to the receptor HasR. However, DHasA can efficiently transfer its heme to the monomeric form that, in turn, delivers it to HasR. We assume that DHasA can function as a heme reservoir in the hemophore system. (c) 2006 Elsevier Ltd. All rights reserved.