The siderocalin/enterobactin interaction: a link between mammalian immunity and bacterial iron transport.
The siderocalin/enterobactin interaction: a link between mammalian immunity and bacterial iron transport.
复制标题
Siderocalin/entobactin的相互作用：哺乳动物免疫与细菌铁转运之间的联系。
DOI：
10.1021/ja803524w
复制
发表时间：
2008-08-27
影响因子：
15
通讯作者：
Raymond, Kenneth N.
中科院分区：
文献类型：
--
作者：
Abergel, Rebecca J.;Clifton, Matthew C.;Pizarro, Juan C.;Warner, Jeffrey A.;Shuh, David K.;Strong, Roland K.;Raymond, Kenneth N.
铁载体肠杆菌素（Ent）由肠道细菌产生以介导铁摄取。Ent清除铁，并被细菌吸收为高度稳定的铁络合物[FeIII（Ent）]3−。该复合物也是哺乳动物先天免疫系统蛋白质Siderocalin（Scn）的特异性靶标，其通过在感染期间特异性螯合铁载体及其铁复合物而充当抗菌剂。最近的文献表明，Scn也可能参与细胞铁的转运，增加了理解Scn拦截和清除铁载体的机制的重要性; Scn被观察到在酸性内体中释放铁，并且已知[FeIII（Ent）]3−在酸性条件下经历从儿茶酚盐到水杨酸盐配位的变化，其被预测为与Scn结合口袋（也称为萼）空间不相容。为了研究铁Ent复合物与Scn在不同pH值下的相互作用，制备了两种在衬于花萼的三个残基中具有突变的重组形式的Scn：Scn-W79 A/R81 A和Scn-Y106 F。Scn-W79 A/R81 A：[FeIII（Ent）]3−和Scn-Y106 F：[FeIII（Ent）]3−复合物的结合研究和晶体结构证实，这些突变不会影响蛋白质的整体构象，但会显著削弱其对[FeIII（Ent）]3−的亲和力。荧光，紫外-可见和EXAFS光谱被用来确定Scn/铁载体解离常数和表征的协调模式的铁在很宽的pH范围内，在突变蛋白和合成水杨酸盐类似物的存在下，而Scn结合阻碍水杨酸盐的协调转换，强酸化的结果在释放铁和降解的铁载体。因此，铁的释放可能是由于Ent降解和协调变化的组合。
The siderophore enterobactin (Ent) is produced by enteric bacteria to mediate iron uptake. Ent scavenges iron and is taken up by the bacteria as the highly stable ferric complex [FeIII(Ent)]3−. This complex is also a specific target of the mammalian innate immune system protein, Siderocalin (Scn), which acts as an anti-bacterial agent by specifically sequestering siderophores and their ferric complexes during infection. Recent literature suggesting that Scn may also be involved in cellular iron transport has increased the importance of understanding the mechanism of siderophore interception and clearance by Scn; Scn is observed to release iron in acidic endosomes and [FeIII(Ent)]3− is known to undergo a change from catecholate to salicylate coordination in acidic conditions, which is predicted to be sterically incompatible with the Scn binding pocket (also referred to as the calyx). To investigate the interactions between the ferric Ent complex and Scn at different pH values, two recombinant forms of Scn with mutations in three residues lining the calyx were prepared: Scn-W79A/R81A and Scn-Y106F. Binding studies and crystal structures of the Scn-W79A/R81A:[FeIII(Ent)]3− and Scn-Y106F:[FeIII(Ent)]3− complexes confirm that such mutations do not affect the overall conformation of the protein but do weaken significantly its affinity for [FeIII(Ent)]3−. Fluorescence, UV-Vis and EXAFS spectroscopies were used to determine Scn/siderophore dissociation constants and to characterize the coordination mode of iron over a wide pH range, in the presence of both mutant proteins and synthetic salicylate analogs of Ent. While Scn binding hinders salicylate coordination transformation, strong acidification results in the release of iron and degraded siderophore. Iron release may therefore result from a combination of Ent degradation and coordination change.
登录
查看更多内容
影响因子：
3.2
作者：
Annamalai, R;Jin, B;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：
15
作者：
Abergel, Rebecca J.;Zawadzka, Anna M.;Raymond, Kenneth N.
通讯作者：
Raymond, Kenneth N.
影响因子：
2.9
作者：
Goetz, DH;Willie, ST;Strong, RK
通讯作者：
Strong, RK
影响因子：
3.5
作者：
Hvidberg, V;Jacobsen, C;Borregaard, N
通讯作者：
Borregaard, N