Structures of Streptococcus pneumoniae PiaA and its complex with ferrichrome reveal insights into the substrate binding and release of high affinity iron transporters.
Structures of Streptococcus pneumoniae PiaA and its complex with ferrichrome reveal insights into the substrate binding and release of high affinity iron transporters.
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肺炎链球菌 PiaA 及其与铁铬复合物的结构揭示了高亲和力铁转运蛋白的底物结合和释放的见解
DOI：
10.1371/journal.pone.0071451
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Cheng W;Li Q;Jiang YL;Zhou CZ;Chen Y
铁缺乏是革兰氏阳性病原体肺炎链球菌在人类宿主中遇到的营养限制之一。为了保证足够的铁供应，ATP结合盒（ABC）转运蛋白Pia被用来摄取由异羟肟酸铁载体螯合的铁，通过膜锚定的底物结合蛋白PiaA。对铁色素的高亲和力使PiaA能够在宿主中以非常低的浓度捕获铁。我们在这里提出的晶体结构的PiaA在载脂蛋白和铁铬络合物的形式在2.7和2.1纳米分辨率，分别。与其他III类底物结合蛋白类似，PiaA由N-末端和C-末端结构域组成，通过α-螺旋桥接。在结构域间裂缝处，铁色素分子由许多高度保守的残基稳定。当铁色素结合时，在裂缝入口处的两个高度柔性的片段经历显著的构象变化，表明它们对铁色素的结合和/或释放的贡献。叠加到大肠杆菌ABC转运蛋白BtuF的结构，使我们能够定义两个保守的残基：Glu 119和Glu 262，这被建议形成盐桥与两个cavinines的通透酶亚基。进一步的基于结构的序列比对显示，铁色素结合模式是高度保守的一系列的PiaA同系物编码的革兰氏阳性和阴性细菌，这被预测为敏感的albomycin，铁霉素抗生素衍生自铁色素。
Iron scarcity is one of the nutrition limitations that the Gram-positive infectious pathogens Streptococcus pneumoniae encounter in the human host. To guarantee sufficient iron supply, the ATP binding cassette (ABC) transporter Pia is employed to uptake iron chelated by hydroxamate siderophore, via the membrane-anchored substrate-binding protein PiaA. The high affinity towards ferrichrome enables PiaA to capture iron at a very low concentration in the host. We presented here the crystal structures of PiaA in both apo and ferrichrome-complexed forms at 2.7 and 2.1 Å resolution, respectively. Similar to other class III substrate binding proteins, PiaA is composed of an N-terminal and a C-terminal domain bridged by an α-helix. At the inter-domain cleft, a molecule of ferrichrome is stabilized by a number of highly conserved residues. Upon ferrichrome binding, two highly flexible segments at the entrance of the cleft undergo significant conformational changes, indicating their contribution to the binding and/or release of ferrichrome. Superposition to the structure of Escherichia coli ABC transporter BtuF enabled us to define two conserved residues: Glu119 and Glu262, which were proposed to form salt bridges with two arginines of the permease subunits. Further structure-based sequence alignment revealed that the ferrichrome binding pattern is highly conserved in a series of PiaA homologs encoded by both Gram-positive and negative bacteria, which were predicted to be sensitive to albomycin, a sideromycin antibiotic derived from ferrichrome.
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DOI：
10.1073/pnas.90.22.10653
发表时间：
1993-11-15
影响因子：
11.1
作者：
LIU, J;RUTZ, JM;KLEBBA, PE
通讯作者：
KLEBBA, PE
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.6
作者：
Brown, JS;Gilliland, SM;Holden, DW
通讯作者：
Holden, DW
影响因子：
2.9
作者：
Killmann, H;Gestwa, G
通讯作者：
Gestwa, G
影响因子：
14.9
作者：
CORPET, F
通讯作者：
CORPET, F