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结核分枝杆菌 DosR 调节子基因 Rv0079 编码一个假定的“休眠相关翻译抑制剂(DATIN)”。

Mycobacterium tuberculosis DosR regulon gene Rv0079 encodes a putative, 'dormancy associated translation inhibitor (DATIN)'.

机构信息

Pathogen Biology Laboratory, Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, India.

出版信息

PLoS One. 2012;7(6):e38709. doi: 10.1371/journal.pone.0038709. Epub 2012 Jun 13.

Abstract

Mycobacterium tuberculosis is a major human pathogen that has evolved survival mechanisms to persist in an immune-competent host under a dormant condition. The regulation of M. tuberculosis metabolism during latent infection is not clearly known. The dormancy survival regulon (DosR regulon) is chiefly responsible for encoding dormancy related functions of M. tuberculosis. We describe functional characterization of an important gene of DosR regulon, Rv0079, which appears to be involved in the regulation of translation through the interaction of its product with bacterial ribosomal subunits. The protein encoded by Rv0079, possibly, has an inhibitory role with respect to protein synthesis, as revealed by our experiments. We performed computational modelling and docking simulation studies involving the protein encoded by Rv0079 followed by in vitro translation and growth curve analysis experiments, involving recombinant E. coli and Bacille Calmette Guérin (BCG) strains that overexpressed Rv0079. Our observations concerning the interaction of the protein with the ribosomes are supportive of its role in regulation/inhibition of translation. We propose that the protein encoded by locus Rv0079 is a 'dormancy associated translation inhibitor' or DATIN.

摘要

结核分枝杆菌是一种主要的人类病原体,它已经进化出生存机制,以在休眠状态下在免疫功能正常的宿主中持续存在。潜伏感染期间结核分枝杆菌代谢的调节尚不清楚。休眠存活调节子(DosR 调节子)主要负责编码结核分枝杆菌与休眠相关的功能。我们描述了 DosR 调节子的一个重要基因 Rv0079 的功能特征,该基因似乎通过其产物与细菌核糖体亚基的相互作用参与翻译的调节。Rv0079 编码的蛋白可能具有抑制蛋白质合成的作用,这是我们实验揭示的。我们进行了涉及 Rv0079 编码蛋白的计算建模和对接模拟研究,随后进行了涉及重组大肠杆菌和卡介苗(BCG)菌株的体外翻译和生长曲线分析实验,这些菌株过表达了 Rv0079。我们观察到该蛋白与核糖体的相互作用支持了其在翻译调节/抑制中的作用。我们提出,Rv0079 基因座编码的蛋白是一种“休眠相关翻译抑制剂”或 DATIN。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1a/3374827/f32aa0757dc6/pone.0038709.g001.jpg

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