Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc
Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc
复制标题
化脓性链球菌转运蛋白 AdcA 中的两个锌结合域促进锌的高亲和力结合和快速转运。
DOI：
10.1074/jbc.m117.818997
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发表时间：
2018-04-20
影响因子：
4.8
通讯作者：
Sun, Xuesong
中科院分区：
文献类型：
--
作者：
Cao, Kun;Li, Nan;Sun, Xuesong
锌是细菌中的一种必需金属。一种重要的细菌锌转运蛋白是AdcA，并且大多数细菌具有AdcA同源物，其是单结构域小蛋白，这是由于更好的蛋白质生物合成效率。然而，具有两个锌结合位点的双结构域AdcA在链球菌属物种中显著过量，其中许多是主要的人类病原体。使用分子模拟和实验验证的AdcA从化脓性链球菌，我们发现在这里，两个AdcA结构域依次稳定锌结合后的结构，表明组织所需的增加锌亲和力和转移速度。这种结构组织似乎赋予链球菌物种在锌耗尽的环境中具有独特的优势，这是不能单独通过每个单个AdcA结构域实现的。这种增强的锌转运机制揭示了AdcA结构域融合进化的重要性，为双结构域转运蛋白与同一离子的两个结合位点提供了新的见解，并指示了抗病原性链球菌物种的抗菌药物的潜在靶点。
Zinc is an essential metal in bacteria. One important bacterial zinc transporter is AdcA, and most bacteria possess AdcA homologs that are single-domain small proteins due to better efficiency of protein biogenesis. However, a double-domain AdcA with two zinc-binding sites is significantly overrepresented in Streptococcus species, many of which are major human pathogens. Using molecular simulation and experimental validations of AdcA from Streptococcus pyogenes, we found here that the two AdcA domains sequentially stabilize the structure upon zinc binding, indicating an organization required for both increased zinc affinity and transfer speed. This structural organization appears to endow Streptococcus species with distinct advantages in zinc-depleted environments, which would not be achieved by each single AdcA domain alone. This enhanced zinc transport mechanism sheds light on the significance of the evolution of the AdcA domain fusion, provides new insights into double-domain transporter proteins with two binding sites for the same ion, and indicates a potential target of antimicrobial drugs against pathogenic Streptococcus species.