锌依赖型 MarR 家族转录调控因子 AdcR 在 Zn(II)结合态下的晶体结构。
Crystal structure of the zinc-dependent MarR family transcriptional regulator AdcR in the Zn(II)-bound state.
机构信息
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
出版信息
J Am Chem Soc. 2011 Dec 14;133(49):19614-7. doi: 10.1021/ja2080532. Epub 2011 Nov 21.
Abstract
Streptococcus pneumoniae adhesin competence regulator (AdcR), the first metal-dependent member of the multiple antibiotic resistance regulator (MarR) family of proteins, represses the transcription of a high-affinity zinc-specific uptake transporter, a group of surface antigen zinc-binding pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE), and an AdcA homologue (AdcAII). The 2.0 Å resolution structure of Zn(II)-bound AdcR reveals a highly helical two-fold-symmetric dimer with two distinct metal-binding sites per protomer. Zn(II) is tetrahedrally coordinated by E24, H42, H108, and H112 in what defines the primary sensing site in AdcR. Site 2 is a tetracoordinate site whose function is currently unknown. NMR methyl group perturbation experiments reveal that Zn(II) drives a global change in the structure of apo-AdcR that stabilizes a conformation that is compatible with DNA binding. This co-repression mechanism is unprecedented in MarR transcriptional regulators.
摘要
肺炎链球菌黏附素反应调节蛋白（AdcR）是多重抗生素耐药调节蛋白（MarR）家族中第一个依赖金属的成员，它可以抑制高亲和力锌特异性摄取转运蛋白、一组表面抗原锌结合肺炎链球菌组氨酸三肽蛋白（PhtA、PhtB、PhtD 和 PhtE）以及 AdcA 同源物（AdcAII）的转录。Zn(II)结合的 AdcR 的 2.0 Å 分辨率结构揭示了一个高度螺旋的二倍对称二聚体，每个亚基具有两个不同的金属结合位点。Zn(II)与 E24、H42、H108 和 H112 配位，形成四面体，这一定义了 AdcR 中的主要感应位点。第二个位点是四配位位点，其功能目前尚不清楚。NMR 甲基基团扰动实验表明，Zn(II)驱动 apo-AdcR 的全局结构变化，稳定了一种与 DNA 结合相容的构象。这种共抑制机制在 MarR 转录调节因子中是前所未有的。
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