Crystal structure of Dps-1, a functionally distinct Dps protein from Deinococcus radiodurans
Crystal structure of Dps-1, a functionally distinct Dps protein from Deinococcus radiodurans
复制标题
DOI：
10.1016/j.jmb.2006.06.010
复制
发表时间：
2006-08-04
影响因子：
5.6
通讯作者：
Lee, Yong-Hwan
中科院分区：
文献类型：
--
作者：
Kim, Song-Gun;Bhattacharyya, Gargi;Lee, Yong-Hwan
饥饿期间DNA保护（Dps）蛋白在保护细胞大分子免受活性氧（ROS）损伤中起重要作用。与大多数直系同源物不同，其通过DNA结合和通过亚铁氧化和螯合铁防止羟基自由基形成的组合来保护DNA，来自耐辐射的耐辐射异常球菌的Dps-1未能通过推断为涉及从蛋白质核心连续释放铁的机制来保护DNA免受羟基自由基介导的切割。为了解决这种不寻常的Fe释放的结构基础，D.抗放射性核素Dps-1的测定分辨率为2.0埃。四个强异常信号每个蛋白质亚基中的两个对应于铁吸收通道和铁氧化酶位点内的金属结合位点，这些共同特征与Dps同源物的典型功能有关。与乳酸乳杆菌Dps类似，在N-末端区域发现金属结合位点。与其他金属位点不同，该位点位于十二聚体蛋白质球外表面上的N-末端螺旋的基部，并且不涉及蛋白质亚基的对称缔合。有趣的是，一个独特的通道状结构被认为具有第四个金属配位位点，这是由蛋白质亚基通过α 2螺旋的3倍对称缔合产生的。这个金属结合位点的存在表明，它可能定义了一个负责从蛋白质核心持续释放铁的铁出口通道。这一解释得到了参与该离子配位的残基的取代以及所得突变蛋白表现出显着减弱的铁释放的观察结果的支持。因此，我们建议D. radiodurans Dps-1具有独特的铁出口通道。(c)2006爱思唯尔有限公司保留所有权利。
DNA protection during starvation (Dps) proteins play an important role in protecting cellular macromolecules from damage by reactive oxygen species (ROS). Unlike most orthologs that protect DNA by a combination of DNA binding and prevention of hydroxyl radical formation by ferroxiciation and sequestration of iron, Dps-1 from the radiation-resistant Deinococcus radiodurans fails to protect DNA from hydroxyl radical-mediated cleavage through a mechanism inferred to involve continuous release of iron from the protein core. To address the structural basis for this unusual release of Fe, the crystal structure of D. radiodurans Dps-1 was determined to 2.0 angstrom resolution. Two of four strong anomalous signals per protein subunit correspond to metal-binding sites within an iron-uptake channel and a ferroxidase site, common features related to the canonical functions of Dps homologs. Similar to Lactobacillus lactis Dps, a metal-binding site is found at the N-terminal region. Unlike other metal sites, this site is located at the base of an N-terminal coil on the outer surface of the dodecameric protein sphere and does not involve symmetric association of protein subunits. Intriguingly, a unique channel-like structure is seen featuring a fourth metal coordination site that results from 3-fold symmetrical association of protein subunits through alpha 2 helices. The presence of this metal-binding site suggests that it may define an iron-exit channel responsible for the continuous release of iron from the protein core. This interpretation is supported by substitution of residues involved in this ion coordination and the observation that the resultant mutant protein exhibits significantly attenuated iron release. Therefore, we propose that D. radiodurans Dps-1 has a distinct iron-exit channel. (c) 2006 Elsevier Ltd. All rights reserved.