Folding and Self-Assembly of the TatA Translocation Pore Based on a Charge Zipper Mechanism
Folding and Self-Assembly of the TatA Translocation Pore Based on a Charge Zipper Mechanism
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DOI：
10.1016/j.cell.2012.12.017
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发表时间：
2013-01-17
期刊：
影响因子：
64.5
通讯作者：
Ulrich, Anne S.
中科院分区：
文献类型：
--
作者：
Walther, Torsten H.;Gottselig, Christina;Ulrich, Anne S.
我们提出了一种基于静电“电荷拉链”的双精氨酸转位酶和其他膜蛋白的折叠和自组装成孔的TatA复合物的概念。TatA的每个亚基由一个跨膜段、一个两亲螺旋（APH）和一个c端密荷区（DCR）组成。DCR中的电荷序列与APH上的电荷模式是互补的，这表明这种蛋白质可以通过七个盐桥组成的阶梯“拉上拉链”。发夹的长度与脂质双分子层的厚度相匹配，因此跨膜孔可以通过分子内和分子间的盐桥自组装。通过分子动力学模拟验证了该方法的空间可行性，并通过监测特定电荷突变体的单体-寡聚平衡获得了实验证据。类似的“电荷拉链”也适用于其他膜相关蛋白，如生物膜诱导肽TisB、人类抗菌肽dermcidin和鼠疫病毒E-RNS蛋白。
We propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic "charge zippers." Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR). The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be "zipped up" by a ladder of seven salt bridges. The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges. The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants. Similar "charge zippers" are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral E-RNS protein.