Ferritin structure from Mycobacterium tuberculosis: comparative study with homologues identifies extended C-terminus involved in ferroxidase activity.
Ferritin structure from Mycobacterium tuberculosis: comparative study with homologues identifies extended C-terminus involved in ferroxidase activity.
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DOI：
10.1371/journal.pone.0018570
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发表时间：
2011-04-08
期刊：
影响因子：
3.7
通讯作者：
Tyagi AK
中科院分区：
文献类型：
--
作者：
Khare G;Gupta V;Nangpal P;Gupta RK;Sauter NK;Tyagi AK
铁蛋白被认为是铁储存和解毒过程中的关键角色。长期以来，病原菌的铁获取已被确定为重要的毒力机制。在这里，我们报告了来自结核分枝杆菌 (Mtb) 的铁蛋白的 3.0 Å 晶体结构，注释为细菌铁蛋白 B (BfrB)，结核分枝杆菌是结核病的病原体，而结核病仍然是世界上最致命的疾病之一。与铁蛋白家族的其他成员类似，Mtb BfrB 亚基表现出具有亚铁氧化酶催化中心的四螺旋束的特征折叠。我们将 Mtb BfrB 的结构与属于古细菌、真细菌和真核生物的铁蛋白家族的代表进行了比较。与大多数其他铁蛋白不同，Mtb BfrB 具有延长的 C 末端。为了剖析这个延伸的 C 末端的作用，纯化了截短的 Mtb BfrB，生化研究表明该区域除了为蛋白质提供稳定性外，还参与亚铁氧化酶活性和铁释放。已知 3D 结构的蛋白质中功能重要的区域可以通过估计氨基酸位点及其密切同源物的保守程度来确定。基于比较研究，我们确定了缓慢进化的保守位点以及快速进化的可变位点，并分析了它们在 Mtb BfrB 结构和功能中的作用。此外，静电计算表明，尽管催化残基的静电环境在该家族中得以保留，但定义通道和孔的残基表现出广泛的可变性，很可能与这些铁蛋白在不同环境中执行的不同功能保持一致。
Ferritins are recognized as key players in the iron storage and detoxification processes. Iron acquisition in the case of pathogenic bacteria has long been established as an important virulence mechanism. Here, we report a 3.0 Å crystal structure of a ferritin, annotated as Bacterioferritin B (BfrB), from Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis that continues to be one of the world's deadliest diseases. Similar to the other members of ferritin family, the Mtb BfrB subunit exhibits the characteristic fold of a four-helical bundle that possesses the ferroxidase catalytic centre. We compare the structure of Mtb BfrB with representatives of the ferritin family belonging to the archaea, eubacteria and eukarya. Unlike most other ferritins, Mtb BfrB has an extended C-terminus. To dissect the role of this extended C-terminus, truncated Mtb BfrB was purified and biochemical studies implicate this region in ferroxidase activity and iron release in addition to providing stability to the protein. Functionally important regions in a protein of known 3D-structure can be determined by estimating the degree of conservation of the amino-acid sites with its close homologues. Based on the comparative studies, we identify the slowly evolving conserved sites as well as the rapidly evolving variable sites and analyze their role in relation to structure and function of Mtb BfrB. Further, electrostatic computations demonstrate that although the electrostatic environment of catalytic residues is preserved within the family, extensive variability is exhibited by residues defining the channels and pores, in all likelihood keeping up with the diverse functions executed by these ferritins in varied environments.
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影响因子：
5.8
作者：
Glaser, F;Pupko, T;Ben-Tal, N
通讯作者：
Ben-Tal, N
DOI：
10.1107/s0907444997003314
发表时间：
1997-09-01
影响因子：
2.2
作者：
Granier, T;Gallois, B;Precigoux, G
通讯作者：
Precigoux, G
影响因子：
3
作者：
Chasteen, ND;Harrison, PM
通讯作者：
Harrison, PM
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
14.9
作者：
Chenna, R;Sugawara, H;Thompson, JD
通讯作者：
Thompson, JD