MadR1, a Mycobacterium tuberculosis cell cycle stress response protein that is a member of a widely conserved protein class of prokaryotic, eukaryotic and archeal origin.

MadR1, a Mycobacterium tuberculosis cell cycle stress response protein that is a member of a widely conserved protein class of prokaryotic, eukaryotic and archeal origin.
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MADR1,一种结核分枝杆菌细胞周期应力反应蛋白,是广泛保守的原核生物,真核和弓形的蛋白质类别的成员。

DOI:
10.1016/j.tube.2015.03.005
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发表时间:
2015-05
期刊:
Tuberculosis (Edinburgh, Scotland)
影响因子:
--
通讯作者:
Slayden RA
Slayden RA
中科院分区:
其他
文献类型:
--
作者:
Crew R;Ramirez MV;England K;Slayden RA

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压力诱导的旨在阻止分裂进程的分子程序在细菌中几乎无处不在,一个众所周知的例子是苏拉隔膜抑制蛋白参与SOS DNA损伤修复反应。分枝杆菌同样表现出应激改变的生长动力学,然而在这些生物体中没有发现这样的调节剂。因此,我们着手确定SulA样调节蛋白在结核分枝杆菌。基于生物信息学建模的方法导致将rv 2216鉴定为编码与苏拉具有弱相似性的蛋白质,进一步分析将该蛋白质区分为属于一组先前未表征的生长促进蛋白。我们将rv 2216形态改变分裂调节蛋白1编码的分枝杆菌蛋白命名为MadR 1。madR 1的过表达调节细胞长度,同时保持与野生型相似的生长动力学,并增加了弯曲或V形细胞的比例。MadR 1-GFP在细胞伸长(两极)和形态分化(V型)区域的存在表明MadR 1参与表型遗传和纵向细胞生长。全球转录分析表明,MadR 1功能与生长和持久性所需的脂质编辑程序有关。这是第一份报告区分较大类的这些保守的蛋白质从苏拉蛋白质和特征MadR 1对分枝杆菌细胞的影响。
Stress-induced molecular programs designed to stall division progression are nearly ubiquitous in bacteria, with one well-known example being the participation of the SulA septum inhibiting protein in the SOS DNA damage repair response. Mycobacteria similarly demonstrate stress-altered growth kinetics, however no such regulators have been found in these organisms. We therefore set out to identify SulA-like regulatory proteins in Mycobacterium tuberculosis. A bioinformatics modeling-based approach led to the identification of rv2216 as encoding for a protein with weak similarity to SulA, further analysis distinguished this protein as belonging to a group of previously uncharacterized growth promoting proteins. We have named the mycobacterial protein encoded by rv2216 morphology altering division regulator protein 1, MadR1. Overexpression of madR1 modulated cell length while maintaining growth kinetics similar to wild-type, and increased the proportion of bent or V-form cells in the population. The presence of MadR1-GFP at regions of cellular elongation (poles) and morphological differentiation (V-form) suggests MadR1 involvement in phenotypic herterogeneity and longitudinal cellular growth. Global transcriptional analysis indicated that MadR1 functionality is linked to lipid editing programs required for growth and persistence. This is the first report to differentiate the larger class of these conserved proteins from SulA proteins and characterizes MadR1 effects on the mycobacterial cell.
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