Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: possible misannotation of this tubercle bacilli-hemolysin.
Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: possible misannotation of this tubercle bacilli-hemolysin.
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DOI：
10.1186/1472-6807-11-16
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发表时间：
2011-03-28
影响因子：
--
通讯作者：
Gómez A
中科院分区：
文献类型：
--
作者：
Arenas NE;Salazar LM;Soto CY;Vizcaíno C;Patarroyo ME;Patarroyo MA;Gómez A
TlyA蛋白作为结核分枝杆菌（Mycobacterium tuberculosis，M.肺结核）。目前，它在M.结核病已经基于体外结果间接提出。然而，没有证据表明TlyA与结核杆菌在宿主细胞内的存活有关，也没有证据表明这两种活性在功能上是否相关。在这项研究中，对这种分枝杆菌蛋白质的结构预测进行了彻底的分析，表明需要重新评估TlyA的毒力功能。TlyA的生物信息学分析鉴定了位于残基5和68之间的核糖体蛋白结合结构域（S4结构域）以及包含残基62和247的FtsJ样甲基转移酶结构域，所有这些结构域先前都已在翻译机器相关蛋白中描述。亚细胞定位预测表明，TlyA缺乏信号肽，其疏水性曲线显示没有跨膜螺旋的证据。这些发现表明，它可能不附着在膜上，这与细胞质定位一致。TlyA的三维建模显示了共有结构，具有由两个α-螺旋层之间的六链β-折叠形成的共同核心，这与RNA甲基转移酶结构一致。系统发育分析表明，分枝杆菌属物种之间的tlyA基因高度保守。此外，核苷酸取代率表明在tlyA基因进化过程中的纯化选择和TlyA蛋白和细菌成孔蛋白之间没有共同的祖先。总而言之，我们的人工计算机策展表明TlyA参与核糖体生物发生，并且在几种微生物和植物基因组中存在关于该蛋白质家族的功能注释错误，包括M.结核病基因组
The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis (M. tuberculosis). At present, its dual activity as hemolysin and RNA methyltransferase in M. tuberculosis has been indirectly proposed based on in vitro results. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether both activities are functionally linked. A thorough analysis of structure prediction for this mycobacterial protein in this study shows the need for reevaluating TlyA's function in virulence. Bioinformatics analysis of TlyA identified a ribosomal protein binding domain (S4 domain), located between residues 5 and 68 as well as an FtsJ-like methyltranferase domain encompassing residues 62 and 247, all of which have been previously described in translation machinery-associated proteins. Subcellular localization prediction showed that TlyA lacks a signal peptide and its hydrophobicity profile showed no evidence of transmembrane helices. These findings suggested that it may not be attached to the membrane, which is consistent with a cytoplasmic localization. Three-dimensional modeling of TlyA showed a consensus structure, having a common core formed by a six-stranded β-sheet between two α-helix layers, which is consistent with an RNA methyltransferase structure. Phylogenetic analyses showed high conservation of the tlyA gene among Mycobacterium species. Additionally, the nucleotide substitution rates suggested purifying selection during tlyA gene evolution and the absence of a common ancestor between TlyA proteins and bacterial pore-forming proteins. Altogether, our manual in silico curation suggested that TlyA is involved in ribosomal biogenesis and that there is a functional annotation error regarding this protein family in several microbial and plant genomes, including the M. tuberculosis genome.
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Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
影响因子：
3.9
作者：
Aravind, L;Koonin, EV
通讯作者：
Koonin, EV
DOI：
10.1016/j.bbrc.2007.06.027
发表时间：
2007-08-24
影响因子：
3.1
作者：
Chou, Kuo-Chen;Shen, Hong-Bin
通讯作者：
Shen, Hong-Bin
影响因子：
4.4
作者：
Felnagle, Elizabeth A.;Rondon, Michelle R.;Thomas, Michael G.
通讯作者：
Thomas, Michael G.
DOI：
10.1093/protein/13.12.839
发表时间：
2000-12-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Innis, CA;Shi, JY;Blundell, TL
通讯作者：
Blundell, TL