The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy.
The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy.
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DOI：
10.3389/fimmu.2018.02086
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发表时间：
2018
影响因子：
7.3
通讯作者：
Sironi M
中科院分区：
文献类型：
--
作者：
Mozzi A;Forni D;Clerici M;Cagliani R;Sironi M
铁是大多数生物物种必需的微量营养素。在哺乳动物中，血红蛋白 (Hb) 储存了体内三分之二以上的铁含量。在血液中，结合珠蛋白 (Hp) 和血红素结合蛋白 (Hpx) 隔离游离的血红蛋白或血红素。病原微生物通常从宿主那里获取铁，并进化出复杂的铁盗版系统来规避营养免疫。在此，我们对病原体物种中编码哺乳动物血红素结合蛋白和血红素清除剂的基因进行了进化分析。基本假设是这些分子正在进行分子军备竞赛。我们证明正选择驱动了哺乳动物 Hb 和 Hpx 的进化。 Hb 中的正选位点位于与脑膜炎奈瑟菌血红素清除剂 HpuA 和金黄色葡萄球菌铁调节表面决定簇 B (IsdB) 的相互作用表面。反过来，HpuA 和 IsdB 中的正选位点位于与 Hb 接触的柔性蛋白质区域。 Hb 中的残基 (S45H) 也在 Caprinae 分支上被选择。该位点可稳定与布氏锥虫血红蛋白触珠蛋白 (HbHp) 受体 (TbHpHbR) 的相互作用，TbHpHbR 是一种也介导锥虫裂解因子 (TLF) 进入的分子。在 TbHpHbR 中，正选择驱动了变体 (L210S) 的进化，该变体允许逃避 TLF，但降低了对 HbHp 的亲和力。最后，Hpx 中的选定位点位于与流感嗜血杆菌血细胞 HxuA 的相互作用表面，而 HxuA 又在 Hpx 结合界面处显示快速进化的位点。这些结果揭示了宿主与病原体的冲突，并确立了营养免疫作为进化力量的重要性。
Iron is an essential micronutrient for most living species. In mammals, hemoglobin (Hb) stores more than two thirds of the body's iron content. In the bloodstream, haptoglobin (Hp) and hemopexin (Hpx) sequester free Hb or heme. Pathogenic microorganisms usually acquire iron from their hosts and have evolved complex systems of iron piracy to circumvent nutritional immunity. Herein, we performed an evolutionary analysis of genes coding for mammalian heme-binding proteins and heme-scavengers in pathogen species. The underlying hypothesis is that these molecules are engaged in a molecular arms race. We show that positive selection drove the evolution of mammalian Hb and Hpx. Positively selected sites in Hb are located at the interaction surface with Neisseria meningitidis heme scavenger HpuA and with Staphylococcus aureus iron-regulated surface determinant B (IsdB). In turn, positively selected sites in HpuA and IsdB are located in the flexible protein regions that contact Hb. A residue in Hb (S45H) was also selected on the Caprinae branch. This site stabilizes the interaction with Trypanosoma brucei hemoglobin-haptoglobin (HbHp) receptor (TbHpHbR), a molecule that also mediates trypanosome lytic factor (TLF) entry. In TbHpHbR, positive selection drove the evolution of a variant (L210S) which allows evasion from TLF but reduces affinity for HbHp. Finally, selected sites in Hpx are located at the interaction surface with the Haemophilus influenzae hemophore HxuA, which in turn displays fast evolving sites at the Hpx-binding interface. These results shed light into host-pathogens conflicts and establish the importance of nutritional immunity as an evolutionary force.
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DOI：
10.1099/mic.0.036475-0
发表时间：
2010-05
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Evans NJ;Harrison OB;Clow K;Derrick JP;Feavers IM;Maiden MCJ
通讯作者：
Maiden MCJ
影响因子：
6.5
作者：
Goheen MM;Campino S;Cerami C
通讯作者：
Cerami C
DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
4.8
作者：
Dickson, Claire F.;Kumar, Kaavya Krishna;Gell, David A.
通讯作者：
Gell, David A.
影响因子：
4.5
作者：
Barber, Matthew F.;Kronenberg, Zev;Elde, Nels C.
通讯作者：
Elde, Nels C.