Structural insights into the complex of trigger factor chaperone and ribosomal protein S7 from Mycobacterium tuberculosis
Structural insights into the complex of trigger factor chaperone and ribosomal protein S7 from Mycobacterium tuberculosis
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结核分枝杆菌触发因子伴侣和核糖体蛋白 S7 复合物的结构见解
DOI：
10.1016/j.bbrc.2019.03.166
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发表时间：
2019-05-14
影响因子：
3.1
通讯作者：
Li, Jixi
中科院分区：
文献类型：
--
作者：
Li, Zhengyang;Wu, Di;Li, Jixi
结核病是由结核分枝杆菌（Mycobacterium tuberculosis，Mtb）引起的一种严重危害人类健康的疾病。结核分枝杆菌的伴侣触发因子（chaperone trigger factor，mtbTF）是一种核糖体相关分子，在共翻译新生链折叠和翻译后蛋白质组装中起重要作用。然而，由于缺乏结构信息，mtbTF的动态调控机制仍然很少调查。本文报道了结核分枝杆菌TF与核糖体蛋白S7（mtbS 7）复合物的结构基础。在体外获得了高纯度和均一性的mtbTF-mtbS 7复合物。MtbTF与mtbS 7结合的Kd值为1.433 μ M，并与mtbS 7以1：2 M的比例形成复合物，如等温滴定量热法所示。此外，mtbS 7的晶体结构被解析到1.8 A的分辨率，其由六个α-螺旋和两个β-链组成。此外，通过小角X射线散射方法构建了mtbTF和mtbTF-mtbS 7复合物的分子包膜，并与这些同源结构相一致。本研究结果为进一步了解TF参与结核分枝杆菌蛋白质折叠和核糖体组装的分子机制提供了结构基础。(C)2019爱思唯尔公司All rights reserved.
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), has threaten human health for thousands years. The chaperone trigger factor (TF) of Mtb (mtbTF), a ribosome-associated molecule, plays important roles in co-translational nascent chain folding and post-translational protein assembly. However, due to lack of structural information, the dynamic regulatory mechanism of mtbTF remains barely investigated. Herein we report the structural basis of the complex of TF and ribosomal protein S7 (mtbS7) from Mtb. The mtbTF-mtbS7 complex was obtained with high purity and homogeneity in vitro. MtbTF bound with mtbS7 in a K-d value of 1.433 mu M, and formed a complex with mtbS7 at 1:2 M ratios as shown by isothermal titration calorimetry. In addition, the crystal structure of mtbS7 was solved to a resolution at 1.8 A, which was composed of six alpha-helices and two beta-strands. Moreover, the molecular envelopes of mtbTF and mtbTF-mtbS7 complex were built and consisted with these homologous structures by small angle X-ray scattering method. Our current findings might provide structural basis for understanding the molecular mechanism of TF in protein folding and the regulation of ribosomal assembly in Mtb. (C) 2019 Elsevier Inc. All rights reserved.